Application of angiotensin converting enzyme inhibitor

[0034] Example 1 Fosinopril can inhibit obesity induced by high-fat diet

[0035] In order to verify the anti-obesity effect of ACE inhibitors, we prepared the following high-fat diet-induced obesity mouse model: 6-week-old C57BL/6J male mice were fed 60Kcal% high-fat diet (Research diet, D12451 ), record weight every week. After 8 weeks of induction and obesity, the high-fat diet induced obesity group was randomly divided into obese control group (HFD, 10) and obese fosinopril group (HFD+ACEI, 14); then obese fosinopril group , Treated with Fosinopril, administered at a dose of 134mg/10kg/day (equivalent to 1.34mg/kg body weight/day); the obese control group and the normal diet group (7 animals, LFD, fed 10Kcal% low Fat feed, Research diet, D12450B), treated with the same dose of starch, administered by mixing into the feed, and continuously administered. The average daily food intake of each experimental group of animals was measured in the first 2 weeks of administration, and the Record your weight every week. After 10 weeks of continuous administration, the mice were sacrificed by cervical dislocation, and the liver, epididymal fat and subcutaneous fat were taken out and weighed.

[0036] The result is Figure 2-4 As shown, figure 2 It shows that fosinopril treatment can effectively inhibit the obesity induced by high-fat diet, and this effect can appear from the first week of fosinopril treatment to the tenth week of the end of the experiment, the maximum difference in body weight, specifically obesity The control group was 46.02±2.5g, the obese fosinopril group was 40.45±3.9g, p <0.001.

[0037] image 3 It shows that compared with the obese control group, the weight percentage of body fat in the fosinopril treatment group decreased by about 13%.

[0038] Figure 4 Show that the treatment of fosinopril reduces the body’s fat deposits, especially significantly reduces the weight of liver and subcutaneous fat (p <0.01).

[0039] Example 2 Fosinopril can improve insulin resistance induced by high-fat diet

[0040] Many research results show that obesity is often accompanied by severe insulin resistance; for this reason, we took the mice at the 9th week of administration in Example 1, and conducted the following experiments:

[0041] 1. Intraperitoneal glucose tolerance test (intraperitoneal glucose tolerance test, IPGTT): the mice after 10 weeks of administration in Example 1 were fasted overnight, after weighing, intraperitoneal injection of glucose 1.5g/kg body weight, after injection, blood glucose The instrument measures blood glucose at 0min, 15min, 30min, 45min, 60min, 90min and 120min.

[0042] The result is Figure 5 As shown, the fasting blood glucose (8.51±1.46mM) of the obesity control group induced by the high-fat diet was significantly higher than that of the normal diet group (6.35±0.73mM), and the treatment of fosinopril can effectively restore the high-fat diet induction Hyperglycemia (6.83±0.98mM, p <0.05); and draw the area under the curve of the glucose tolerance test, the results are as follows Image 6 As shown, it indicates that Fosinopril can significantly improve the clearance of blood sugar (p <0.05).

[0043] 2. Insulin tolerance test (ITT): The mice after 10 weeks of administration in Example 1 were fasted for 6 hours, weighed and injected with insulin 1IU/kg body weight in the abdominal cavity. After the injection, use a blood glucose meter Blood glucose was measured at 0min, 5min, 30min, 45min, 60min, 90min and 120min respectively.

[0044] The result is Figure 7 This indicates that Fosinopril can significantly improve insulin sensitivity.

[0045] All in all, from Figure 5-7 As a result, it can be seen that Fosinopril can improve insulin resistance induced by a high-fat diet.

[0046] Example 3 Fosinopril can improve energy consumption

[0047] Take the mice after the 10th week of administration in Example 1, measure their oxygen consumption with LabMaster of TSE Company, and place them under the conditions of 25°C and 4°C to measure the body temperature of the mice.

[0048] The result is Figure 8-9 As shown, it can explain the effect of fosinopril on body weight and insulin sensitivity. by Figure 8 We can see that Fosinopril increases the body’s oxygen consumption, indicating that Fosinopril improves the body’s overall energy metabolism (p <0.05). Not only that, Picture 9 Shows that Fosinopril can effectively improve the fever under cold stimulation (p <0.05).

[0049] In summary, Figure 8-9 The results suggest that Fosinopril can increase the body's energy metabolism.