Nerve regulation device for regulating glucose metabolism

Abstract

The invention belongs to the technical field of glucose metabolism regulation and control, and discloses a nerve regulation and control device for regulating glucose metabolism, which comprises an ultrasonic transducer and a control module, the ultrasonic transducer is used for emitting low-intensity focused ultrasound to the hypothalamic arcuate nucleus so as to carry out ultrasonic stimulation on the hypothalamic arcuate nucleus; the control module is connected with the ultrasonic transducer and is used for adjusting parameters of the low-intensity focused ultrasound emitted by the ultrasonic transducer; the ultrasonic stimulation is formed on the hypothalamic arcuate nucleus by utilizing the low-intensity focused ultrasound emitted by the ultrasonic transducer, and the ultrasonic stimulation directly acts on a nerve regulation center of glucose metabolism in a targeted stimulation manner, so that the aim of regulating glucose metabolism is fulfilled.

Description

Technical Field

[0001] The present invention belongs to the technical field of glucose metabolism regulation, and in particular relates to a neural regulation device for regulating glucose metabolism. Background Art

[0002] Glucose metabolism is crucial for maintaining the body's energy balance and physiological homeostasis. Disturbance in glucose metabolism has become a key pathological feature of diseases such as type 2 diabetes, obesity, and cardiovascular disease. Although existing drug treatments and lifestyle interventions have achieved certain results in some patients, they still cannot meet the treatment needs of all patients due to side effects, poor patient compliance, and limited efficacy.

[0003] Among them, drug treatment can take effect quickly, is convenient and highly targeted, but is often accompanied by side effects and drug resistance problems, and is highly dependent; lifestyle interventions such as exercise and dietary changes can improve health, but they are slow to take effect, difficult to stick to, and the effects vary due to individual differences.

[0004] In recent years, there have been some physical therapy techniques such as electrical stimulation and optogenetics. Although they theoretically have the ability to regulate glucose metabolism, they face great obstacles in clinical application due to their invasiveness and complexity. For example, optogenetics requires genetic modification of neurons and combines it with invasive operations, which greatly reduces the feasibility of its clinical application. Summary of the invention

[0005] In view of the technical problems existing in the prior art, the present invention provides a neural control device for regulating glucose metabolism, which solves the technical problems that the existing means of regulating glucose metabolism are invasive operations and cannot be precisely controlled.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is: The present invention provides a neural control device for regulating glucose metabolism, comprising an ultrasonic transducer and a control module; the ultrasonic transducer is used to emit low-intensity focused ultrasound to the arcuate nucleus of the hypothalamus to perform ultrasonic stimulation on the arcuate nucleus of the hypothalamus; the control module is connected to the ultrasonic transducer and is used to adjust the parameters of the low-intensity focused ultrasound emitted by the ultrasonic transducer.

[0007] Furthermore, the front end of the ultrasonic transducer contacts a preset target position through a coupling water bag; wherein the preset target position corresponds to the arcuate nucleus of the hypothalamus.

[0008] Furthermore, an ultrasonic coupling agent is injected into the coupling water bag; wherein the ultrasonic coupling agent serves as a sound wave conduction medium for low-intensity focused ultrasound.

[0009] Furthermore, the center frequency of the ultrasonic transducer is 0.9-1.1 MHz.

[0010] Furthermore, the pulse duration of the ultrasonic transducer is 2 ms, the pulse repetition frequency is 250 MHz, and the duty cycle is 50%.

[0011] Furthermore, the duration of ultrasound stimulation was 150-250 ms, and the stimulation interval was 4-6 s.

[0012] Furthermore, the sound pressure at the acoustic focus of the ultrasonic transducer is 0.35-0.51 MPa, and the pulse intensity integral is 9.66-14.07 mJ / cm².

[0013] Furthermore, the average intensity of the spatial peak pulse at the acoustic focus of the ultrasonic transducer is 4.83-7.05 W / cm², and the average intensity at the spatial peak is 2.42-3.52 W / cm².

[0014] Furthermore, it also includes a three-dimensional moving device, and the ultrasonic transducer is installed on the three-dimensional moving device; wherein the three-dimensional moving device is used to drive the ultrasonic transducer to move according to a preset stereo positioning coordinate system, and to match the acoustic focus of the ultrasonic transducer with the arcuate nucleus of the hypothalamus.

[0015] Furthermore, the preset stereotactic coordinate system is established with the three-dimensional anatomical landmarks of the anterior fontanelle, the posterior fontanelle and the sagittal suture as spatial geometric features.

[0016] Compared with the prior art, the present invention has the following beneficial effects: The neural control device for regulating glucose metabolism provided by the present invention uses low-intensity focused ultrasound emitted by an ultrasonic transducer to form ultrasonic stimulation to the arcuate nucleus of the hypothalamus, and directly acts on the neural control center of glucose metabolism in a targeted stimulation manner, thereby achieving the purpose of regulating glucose metabolism; secondly, the parameters of the low-intensity focused ultrasound emitted by the ultrasonic transducer are adjusted by a control module, which can effectively improve the accuracy of the ultrasonic stimulation and at the same time enhance the flexibility of use of the device; the device of the present invention has a simple structure, adopts a non-invasive ultrasonic stimulation method, does not require surgical operation, greatly reduces safety risks and improves patients' treatment compliance. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0018] Figure 1 Schematic diagram of the structure of a neural control device for regulating glucose metabolism provided in an embodiment Figure 2 This is the blood glucose change curve result during the glucose tolerance test of mice fed a long-term high-fat diet under low-intensity ultrasound stimulation; Figure 3 The area under the glucose tolerance curve of mice fed a long-term high-fat diet stimulated by low-intensity ultrasound; Figure 4 This is a graph showing fasting plasma glucose levels in mice on a long-term high-fat diet before ultrasound stimulation. Figure 5 This is a graph showing the fasting plasma glucose level in mice on a long-term high-fat diet after ultrasound stimulation. Figure 6 This is a graph showing the blood sugar change curve during the glucose tolerance test of normal mice stimulated by low-intensity ultrasound; Figure 7 The area under the glucose tolerance curve of normal mice stimulated by low-intensity ultrasound.

[0019] Among them, 1 is an ultrasonic transducer, 2 is a three-dimensional moving device, and 3 is a control module. DETAILED DESCRIPTION

[0020] In order to make the technical problems, technical solutions and beneficial effects solved by this application clearer, the technical solutions in the embodiments of this application will be described clearly and completely in combination with the drawings in the embodiments of this application; obviously, the described embodiments are only part of the embodiments of this application, not all of them. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0021] The present invention provides a neuroregulatory device for regulating glucose metabolism, comprising an ultrasonic transducer 1, a three-dimensional mobile device 2 and a control module 3; the ultrasonic transducer 1 is used to emit low-intensity focused ultrasound (LIFU) to the arcuate nucleus of the hypothalamus to perform ultrasonic stimulation on the arcuate nucleus of the hypothalamus; the ultrasonic transducer 1 is installed on the three-dimensional mobile device 2; wherein the three-dimensional mobile device 2 is used to drive the ultrasonic transducer 1 to move according to a preset stereo positioning coordinate system, and to match the acoustic focus of the ultrasonic transducer 1 with the arcuate nucleus of the hypothalamus; the control module 3 is connected to the ultrasonic transducer 1, and is used to adjust the parameters of the low-intensity focused ultrasound emitted by the ultrasonic transducer.

[0022] The neuroregulatory device for regulating glucose metabolism described in the present invention uses low-intensity focused ultrasound emitted by an ultrasonic transducer to form ultrasonic stimulation on the arcuate nucleus of the hypothalamus, so as to utilize non-invasive transcranial ultrasound stimulation technology to accurately target the arcuate nucleus of the hypothalamus, regulate its key role in glucose metabolism, improve glucose tolerance, promote glucose uptake, and restore metabolic balance, thereby avoiding the side effects and drug resistance problems of existing drug treatments and having high safety and effectiveness.

[0023] The following is a further explanation of the neuroregulatory device for regulating glucose metabolism provided by the present invention with reference to specific embodiments, as follows: Example As attached Figure 1 As shown, this embodiment provides a neuroregulatory device for regulating glucose metabolism, including an ultrasonic transducer 1, a three-dimensional moving device 2 and a control module 3; the ultrasonic transducer 1 is installed on the three-dimensional moving device 2, and the ultrasonic transducer 1 is connected to the output end of the control module 3.

[0024] The ultrasonic transducer 1 is used to emit low-intensity focused ultrasound (LIFU) to the arcuate nucleus of the hypothalamus, so as to use the low-intensity focused ultrasound to ultrasonically stimulate the arcuate nucleus of the hypothalamus; wherein the front section of the ultrasonic transducer 1 contacts with a preset target position through a coupling water bag, and the preset target position corresponds to the arcuate nucleus of the hypothalamus; an ultrasonic coupling agent is injected into the coupling water bag, and the ultrasonic coupling agent serves as a sound wave conduction medium of the low-intensity focused ultrasound.

[0025] The three-dimensional moving device 2 is used to drive the ultrasonic transducer 1 to move according to a preset stereotaxic coordinate system, and to match the acoustic focus of the ultrasonic transducer 1 with the arcuate nucleus of the hypothalamus; wherein the preset stereotaxic coordinate system is established with the three-dimensional anatomical landmarks of the anterior fontanelle, the posterior fontanelle and the sagittal suture as spatial geometric features; specifically, the three-dimensional moving device 2 includes a three-dimensional electric system and a three-dimensional operating arm; the input end of the three-dimensional electric system is connected to the output end of the control module 3, and the output end of the three-dimensional electric system is connected to the input end of the three-dimensional operating arm; wherein the three-dimensional electric system is used to respond to the action instructions sent by the control module 3 to drive the three-dimensional operating arm to move; the ultrasonic transducer 1 is installed on the three-dimensional operating arm to move following the action of the three-dimensional operating arm.

[0026] The control module 3 is used to send ultrasonic parameter instructions to the ultrasonic transducer 1 to adjust the parameters of low-intensity focused ultrasound emitted by the ultrasonic transducer; wherein the parameters of low-intensity focused ultrasound include frequency, intensity, duration and stimulation time; the control module 3 is also used to send action instructions to the three-dimensional mobile device 2 to trigger the action of the three-dimensional electric system in the three-dimensional mobile device 2, thereby driving the action of the three-dimensional operating arm in the three-dimensional mobile device.

[0027] In this embodiment, by accurately designing the center frequency, pulse duration, pulse repetition frequency, duty cycle, sound pressure at the acoustic focus, pulse intensity integral, spatial peak pulse average intensity at the acoustic focus, spatial peak time average intensity, as well as ultrasonic stimulation duration and stimulation interval of the ultrasonic transducer 1, it is effectively ensured that while improving glucose metabolism, adverse reactions caused by excessive stimulation are avoided; wherein, the center frequency of the ultrasonic transducer 1 is 0.9-1.1MHz; the pulse duration of the ultrasonic transducer 1 is 2ms, the pulse repetition frequency is 250MHz, and the duty cycle is 50%; the ultrasonic stimulation duration is 150-250ms, and the stimulation interval is 4-6s; the sound pressure at the acoustic focus of the ultrasonic transducer 1 is 0.35-0.51Mpa, and the pulse intensity integral is 9.66-14.07mJ / cm²; the spatial peak pulse average intensity at the acoustic focus of the ultrasonic transducer 1 is 4.83-7.05W / cm², and the spatial peak time average intensity is 2.42-3.52W / cm².

[0028] Working principle: The neuroregulatory device for regulating glucose metabolism described in this embodiment emits low-intensity focused ultrasound to the arcuate nucleus of the hypothalamus, and regulates the activity of neurons in the arcuate nucleus of the hypothalamus by stimulating the arcuate nucleus of the hypothalamus, thereby affecting the secretion of metabolic hormones and achieving the purpose of regulating glucose metabolism. Specifically, low-intensity focused ultrasound is used to directly act on neurons in the arcuate nucleus of the hypothalamus, such as pro-opiomelanocortin (POMC) neurons and agouti-related protein (AgRP) neurons, in a targeted stimulation manner, and the neurons in the arcuate nucleus of the hypothalamus are stimulated by ultrasound to secrete metabolic hormones (such as leptin, insulin, etc.) to regulate glucose metabolism.

[0029] Animal testing verification: (1) Animal model construction Thirty-two five-week-old male C57BL / 6J mice were randomly assigned to a conventional diet (CD) group and a high-fat diet (HFD) group after one week of adaptive feeding. The conventional diet group included 8 mice, which were fed with conventional feed; the high-fat diet group included the remaining 24 mice, which were fed with a high-fat diet, and the feed type was D12492. After 12 weeks of feeding, all mice underwent a one-week adaptive training. The mice in the high-fat diet group were divided into HFD+ and HFD+ groups according to the levels of fasting blood glucose, triglycerides, and total cholesterol. There were 37 mice in the Sham group (n=12) and the HFD+US group (n=12), where n is the number of mice. Then, in the following 4 weeks, the HFD+US group received 15 min of low-intensity focused ultrasound stimulation via the arcuate nucleus of the hypothalamus every day, the HFD+Sham group received a sham treatment procedure without turning on ultrasound transducer 1, and the mice in the CD group did not receive any treatment. After the third week of low-intensity focused ultrasound stimulation, a glucose tolerance test was performed on the mice, and blood samples were collected from the mice 6 hours fasting before the start of the experiment and in the fourth week of the experiment to measure fasting blood glucose.

[0030] Sixteen 8-week-old male C57BL / 6J mice were randomly divided into US group and NC group, with 8 mice in each group; the US group received low-intensity focused ultrasound stimulation via the arcuate nucleus of the hypothalamus for 15 min per day for 5 days; the NC group followed the same experimental procedure but did not receive low-intensity focused ultrasound stimulation via the arcuate nucleus of the hypothalamus; a glucose tolerance test was performed on the 6th day of the experiment.

[0031] The specific process of low-intensity focused ultrasound stimulation of the arcuate nucleus of the hypothalamus is to stimulate the preset ultrasound stimulation points using the neuroregulatory device for regulating glucose metabolism described in this embodiment; the preset ultrasound stimulation points are the arcuate nucleus of the hypothalamus of mice; wherein, according to the stereotaxic map of the mouse brain, the preset ultrasound stimulation point coordinates are AP-1.40mm, ML0.00mm, and DV-5.80 mm.

[0032] Specifically, the process of stimulating the preset ultrasound stimulation points is as follows: First, an ultrasonic coupling agent is used as a sound wave transmission medium; during operation, the ultrasonic coupling agent is injected along the middle hole of the coupling water bag; during the ultrasonic coupling agent infusion process, the liquid level state is observed in real time to eliminate bubble interference in time; after the ultrasonic coupling agent is filled, the collimator is installed in the fixing slot of the carrier arm of the brain stereotaxic instrument to ensure that the neural regulation device forms a stable spatial geometric relationship with the skull positioning marker.

[0033] Next, start the animal water bath constant temperature heating device; in the initial stage, the temperature is set to the equipment limit parameter to quickly heat up, and when the temperature approaches 37°C, the temperature is accurately set to 37°C and maintained constant.

[0034] Afterwards, the oxygen source was turned on, the animal anesthesia system was connected, the isoflurane concentration was adjusted to 2%, and the oxygen flow rate was set to 0.6 L / min. The mice were placed in a closed anesthesia induction box for gas inhalation anesthesia to induce the mice into an anesthesia state.

[0035] Next, the mouse after anesthesia induction was immediately transferred to the operating table of the brain stereotaxic instrument, and its maxillary incisors were engaged with the tooth sockets of the brain stereotaxic instrument. At the same time, the mouth and nose area were tightly covered with an adapted anesthesia mask to maintain the mouse's anesthesia state.

[0036] Afterwards, on the basis of non-invasive intervention, pretreatment is required to ensure positioning accuracy; specifically, the hair on the top of the skull is first removed using a shaving instrument combined with a depilatory agent; then the skin is incised along the midline to fully expose the three-dimensional anatomical landmarks of the anterior fontanelle, posterior fontanelle, and sagittal suture, and finally, based on the spatial geometric characteristics of the three-dimensional anatomical landmarks of the anterior fontanelle, posterior fontanelle, and sagittal suture, the stereotaxic coordinate system marking is completed at the preset ultrasound stimulation point.

[0037] Finally, the ultrasonic transducer 1 is driven to move by a three-dimensional manipulator so that the acoustic focus of the ultrasonic transducer 1 accurately matches the preset coordinates of the ultrasonic stimulation point; then, the ultrasonic coupling agent is evenly applied to the contact part, and the ultrasonic transducer 1 is moved so that the lower edge of the coupling water bag is seamlessly coupled with the mouse skull membrane; then, low-intensity focused ultrasound stimulation is performed according to the preset ultrasonic stimulation parameters; preferably, the preset ultrasonic stimulation parameters are as follows: The center frequency of the ultrasonic transducer 1 is 1.0MHz, the pulse duration is 2ms, the pulse repetition frequency is 250MHz, and the duty cycle is 50%; the ultrasonic stimulation duration is 200ms, and the stimulation interval is 5s; the sound pressure at the acoustic focus of the ultrasonic transducer 1 is 0.43Mpa, and the pulse intensity integral is 11.87mJ / cm²; the spatial peak pulse average intensity at the acoustic focus of the ultrasonic transducer 1 is 5.94W / cm², and the spatial peak time average intensity is 2.97W / cm².

[0038] The specific process of the glucose tolerance test is as follows: (a) Preparation before the experiment: One day before the experiment, the mice were transferred to a clean cage and fasted for 16 h. On the day of the experiment, 15 mL of 200 mg / mL glucose solution was prepared with normal saline. Before the experiment, each mouse was weighed and the volume of glucose to be gavaged was calculated according to a dose of 2 g / kg. (b) Blood glucose collection and data recording: Cut off about 1-2 mm from the end of the mouse's tail, gently squeeze the mouse's tail along the tail vein to enrich the blood into one drop, discard the first drop, and use a blood glucose meter and its matching blood glucose test strips to measure the second drop of blood as the mouse's fasting blood glucose value, that is, the blood glucose value at 0 min; after the mouse stabilizes for a while, gently pick up the mouse and perform gavage according to the calculated gavage glucose volume; finally, at 15 min, 30 min, 60 min, 90 min, and 120 min, measure the blood glucose value of each mouse at each time point according to the measurement operation at 0 min.

[0039] The process of fasting blood sugar measurement is as follows: Sample collection and storage: Each group of mice was fasted but not watered for 6 hours, and the environment was kept quiet during this period; whole blood samples from the tail vein of each group of mice were collected using capillaries, and then immediately placed in an ice box for 30 minutes; the samples were transferred to a capillary blood centrifuge that had been pre-cooled at 4°C for centrifugation; then, transparent plasma was blown out with a micropipette and dispensed into labeled 0.5ml EP tubes, and then quickly transferred to a -80°C ultra-low temperature refrigerator for storage; concentration detection: Glucose oxidase detection kit (Cat. No. 04404483190, Roche) was used for detection; specifically, first, calibration samples were prepared according to Table 1 below; then, the reaction detection solution was prepared; wherein, for a single sample, 28μL of reagent 1, 10μL of reagent 2 and 162μL of ddH 2 O, prepare a total of 200 μL of reaction detection solution; then, add 20 μL of phosphate buffer to the prepared 96-well plate; add the corresponding volume of the prepared calibration sample to the corresponding well; add 7.5 μL of 2-fold diluted serum sample to the corresponding well; add the prepared 200 μL reaction detection solution; then, place it on a microplate oscillator and incubate at room temperature for 30-45 minutes; use an enzyme reader to detect the absorbance, and set the sub / dominant wavelength of the detection to 700 / 340 nm; finally, draw a standard curve, calculate the plasma glucose concentration of each sample, and finally perform data statistics and analysis.

[0040] Table 1 Preparation of calibration samples used to construct the standard curve for glucose detection

[0041] As attached Figure 2-3 As shown, attached Figure 2 The results of the blood glucose change curve during the glucose tolerance test of mice fed a long-term high-fat diet under low-intensity ultrasound stimulation are given in the attached figure. Figure 3 The area under the glucose tolerance curve of mice fed a long-term high-fat diet stimulated by low-intensity ultrasound is given in Figure 2-3 ** represents the hypothesized probability P<0.01, *** represents P<0.001; Figure 2-3 It can be seen that low-intensity focused ultrasound stimulation of the arcuate nucleus of the hypothalamus can improve the abnormal glucose metabolism of obese mice induced by a high-fat diet. Specifically, after glucose loading, the blood glucose peak of the HFD+US group was significantly reduced and the blood glucose change curve was flatter. In addition, the area under the glucose tolerance curve was significantly reduced.

[0042] As attached Figure 4-5 As shown, attached Figure 4 Figure 2 shows the fasting plasma glucose levels of mice fed a long-term high-fat diet before ultrasound stimulation. Figure 5 The figure shows the fasting plasma glucose level of mice on a long-term high-fat diet after ultrasound stimulation; Figure 4-5 ** represents P < 0.01, *** represents P < 0.001, **** represents P < 0.0001; Figure 4-5 It can be seen that long-term high-fat diet can induce abnormal increase in fasting plasma glucose in mice, while low-intensity focused ultrasound stimulation of the hypothalamic arcuate nucleus can reduce fasting blood glucose to normal levels.

[0043] As attached Figure 6-7 As shown, attached Figure 6 The results of the blood glucose change curve during the glucose tolerance test of normal mice stimulated by low-intensity ultrasound are given in the Appendix. Figure 7 The area under the glucose tolerance curve of normal mice stimulated by low-intensity ultrasound is given in Figure 7 * indicates P < 0.05; Figure 6-7 It can be seen that low-intensity focused ultrasound stimulation of the arcuate nucleus of the hypothalamus can improve the glucose metabolism of normal mice. Specifically, after glucose load, the blood glucose peak of the US group was significantly reduced and the blood glucose change curve was flatter. In addition, the area under the glucose tolerance curve was significantly reduced.

[0044] The neuroregulatory device for regulating glucose metabolism described in this embodiment uses non-invasive transcranial ultrasound stimulation technology to accurately target the arcuate nucleus of the hypothalamus, regulate its key role in glucose metabolism, improve glucose tolerance, promote glucose uptake, and restore metabolic balance, thereby avoiding the side effects and drug resistance problems of existing drug treatments and having high safety and effectiveness; secondly, the specific design of the stimulation parameters can ensure that while improving glucose metabolism, adverse reactions caused by excessive stimulation can be avoided.

[0045] The neuroregulatory device described in the present invention utilizes low-intensity focused ultrasound emitted by an ultrasonic transducer to form ultrasonic stimulation to the arcuate nucleus of the hypothalamus, and performs precise and non-invasive stimulation of the arcuate nucleus of the hypothalamus through transcranial ultrasound, which can directly act on the central nervous system to regulate sugar metabolism, and can rapidly improve glucose metabolism, thereby avoiding common side effects and drug resistance problems in drug treatment, and has no drug dependence, reducing the risks and burdens of long-term treatment; the device described in the present invention is completely non-invasive, does not require surgical operation, has lower risks and higher safety, and has a wide range of applications, and can benefit a wider range of patients with diabetes and metabolic diseases.

[0046] In the present invention, the arcuate nucleus of the hypothalamus is stimulated by low-intensity focused ultrasound, without the need for genetic modification or complicated surgery, and can achieve precise regulation of the arcuate nucleus of the hypothalamus without interfering with normal physiological functions, thus avoiding the limitations of optogenetics in clinical applications; wherein, low-intensity focused ultrasound can safely penetrate the skull and accurately regulate the activity of the arcuate nucleus of the hypothalamus, thus avoiding the risks and discomfort of electrical stimulation; by directly acting on the arcuate nucleus of the hypothalamus, it can more comprehensively regulate glucose metabolism; the arcuate nucleus of the hypothalamus plays an important role in glucose metabolism, and by regulating its activity, it can improve glucose metabolism and energy balance at multiple levels, thereby achieving more effective therapeutic effects.

[0047] The above embodiment is only one of the implementation methods that can realize the technical solution of the present invention. The scope of protection claimed by the present invention is not limited only to this embodiment, but also includes changes, replacements and other implementation methods that can be easily thought of by any technician familiar with the technical field within the technical scope disclosed by the present invention.

Claims

1. A neural control device for regulating glucose metabolism, characterized in that: The invention comprises an ultrasonic transducer (1) and a control module (3); the ultrasonic transducer (1) is used to transmit low-intensity focused ultrasound to the arcuate nucleus of the hypothalamus, so as to ultrasonically stimulate the arcuate nucleus of the hypothalamus; the control module (3) is connected to the ultrasonic transducer (1) and is used to adjust the parameters of the low-intensity focused ultrasound transmitted by the ultrasonic transducer.

2. A neural control device for regulating glucose metabolism according to claim 1, characterized in that: The front end of the ultrasonic transducer (1) contacts a preset target position via a coupling water bag; wherein the preset target position corresponds to the arcuate nucleus of the hypothalamus.

3. A neural control device for regulating glucose metabolism according to claim 2, characterized in that: An ultrasonic coupling agent is injected into the coupling water bag; wherein the ultrasonic coupling agent serves as a sound wave conduction medium for low-intensity focused ultrasound.

4. A neural control device for regulating glucose metabolism according to claim 1, characterized in that: The central frequency of the ultrasonic transducer (1) is 0.9-1.1 MHz.

5. A neural control device for regulating glucose metabolism according to claim 4, characterized in that: The ultrasonic transducer (1) has a pulse duration of 2 ms, a pulse repetition frequency of 250 MHz, and a duty cycle of 50%.

6. A neural control device for regulating glucose metabolism according to claim 1, characterized in that: The duration of ultrasound stimulation was 150-250 ms, and the stimulation interval was 4-6 s.

7. A neural control device for regulating glucose metabolism according to claim 1, characterized in that: The sound pressure at the acoustic focus of the ultrasonic transducer (1) is 0.35-0.51 MPa, and the pulse intensity integral is 9.66-14.07 mJ / cm².

8. The neural control device for regulating glucose metabolism according to claim 1, characterized in that: The spatial peak pulse average intensity at the acoustic focus of the ultrasonic transducer (1) is 4.83-7.05 W / cm², and the spatial peak time average intensity is 2.42-3.52 W / cm².

9. A neural control device for regulating glucose metabolism according to claim 1, characterized in that: It also includes a three-dimensional moving device (2), on which the ultrasonic transducer (1) is mounted; wherein the three-dimensional moving device (2) is used to drive the ultrasonic transducer (1) to move according to a preset stereoscopic positioning coordinate system, and to match the acoustic focus of the ultrasonic transducer (1) with the arcuate nucleus of the hypothalamus.

10. The neural control device for regulating glucose metabolism according to claim 1, characterized in that: The preset stereotaxic coordinate system is established with the three-dimensional anatomical landmarks of the anterior fontanelle, the posterior fontanelle and the sagittal suture as spatial geometric features.

Images