Application of alpha-ketoglutaric acid in diagnosis and treatment of acute pancreatitis

Abstract

The invention discloses an application of alpha-ketoglutaric acid in diagnosis and treatment of acute pancreatitis, diagnosis of acute pancreatitis is realized by detecting the concentration of alpha-ketoglutaric acid in serum or plasma of a detected person, and the invention also provides an application of alpha-ketoglutaric acid in preparation of a diagnostic reagent for monitoring the condition of acute pancreatitis. By dynamically detecting the concentration change of alpha-ketoglutaric acid in serum or plasma of a patient, the real-time monitoring of the illness state is realized. The invention discloses the specific accumulation of the endogenous alpha-ketoglutaric acid level in the serum of a patient with acute pancreatitis for the first time, and the endogenous alpha-ketoglutaric acid level is remarkably positively correlated with disease severity indexes (such as amylase and leukocyte count); the invention provides a simple, convenient and effective serological biomarker for early and accurate diagnosis and illness monitoring of acute pancreatitis, and provides a novel treatment strategy with strong targeting property.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically to the application of α-ketoglutarate in the diagnosis and treatment of acute pancreatitis. Background Technology

[0002] Acute pancreatitis (AP) is a clinical acute abdominal condition with rapid onset and progression. Its pathophysiological process is complex, and it can develop from a mild, self-limiting disease into severe acute pancreatitis (SAP) with multiple organ failure, the latter having an extremely high mortality rate. The clinical diagnosis of acute pancreatitis mainly relies on typical medical history, amylase, lipase, and inflammatory marker detection, and imaging examinations. However, the accuracy of these methods in predicting SAP and mortality is not high. Given the importance of early identification and intervention in the diagnosis of acute pancreatitis, there is an urgent clinical need to develop a more accurate and simple indicator to predict and monitor the occurrence and development of acute pancreatitis. On the other hand, the clinical treatment of SAP still mainly focuses on fluid resuscitation, nutritional support, and symptomatic treatment, lacking specific targeted drugs that can target its core pathogenesis. The treatment of pancreatitis remains a challenge.

[0003] α-Ketoglutaric acid (AKG) is a key intermediate in the tricarboxylic acid cycle. It is not only a hub for cellular energy metabolism, but in recent years it has also been discovered to be a signaling molecule with pleiotropic biological functions, playing an important role in regulating inflammation, oxidative stress and autophagy. However, the specific role, mechanism of action and potential of AKG as a therapeutic agent in acute pancreatitis have not yet been elucidated.

[0004] Acute pancreatitis (AP) is a common acute abdominal condition in clinical practice. Its pathogenesis is complex and the disease progresses rapidly. In particular, severe acute pancreatitis (SAP) often leads to multiple organ failure and has an extremely high mortality rate. Therefore, there is an urgent need in this field to develop a more specific and convenient biomarker for the accurate diagnosis and disease monitoring of acute pancreatitis, and to find new and effective therapeutic drugs that can target its core pathophysiological processes. Summary of the Invention

[0005] The purpose of this invention is to provide an application of α-ketoglutarate in the diagnosis and treatment of acute pancreatitis, so as to solve the problems mentioned in the background art.

[0006] To achieve the above objectives, the present invention provides the following technical solution: the application of α-ketoglutarate in the preparation of a diagnostic reagent for diagnosing acute pancreatitis. The diagnosis of acute pancreatitis is achieved by detecting the concentration of α-ketoglutarate in the serum or plasma of the tested subject. Previous clinical studies have found that the level of α-ketoglutarate in the serum or plasma of patients with acute pancreatitis is specifically and significantly elevated. The acute pancreatitis includes, but is not limited to, acute pancreatitis induced by cholelithiasis, hyperlipidemia, alcohol, drugs, or surgical trauma. Pharmaceutically acceptable salts of α-ketoglutarate include its sodium, potassium, calcium, or magnesium salts. The dosage form of the pharmaceutical composition is an oral preparation or an injectable preparation. The oral preparation includes tablets, capsules, granules, oral liquids, etc.; the injectable preparation includes injection solutions and sterile powders for injection.

[0007] Preferably, the application of α-ketoglutarate in the preparation of diagnostic reagents for monitoring acute pancreatitis is also provided, which enables real-time monitoring of the condition by dynamically detecting changes in the concentration of α-ketoglutarate in the patient's serum or plasma.

[0008] The preferred and specific determination principles and methods are detailed below: 1. Determination method in diagnosis: Comparison principle: The core of diagnosis lies in comparing the concentration of α-ketoglutarate in the serum or plasma of the subject with one or more preset reference standards. The reference standards include: 1) the baseline AKG concentration level obtained from statistics of healthy individuals; 2) the AKG concentration level from patients with other non-pancreatitis abdominal emergencies (such as acute cholecystitis) with similar clinical symptoms. Diagnostic basis: When the AKG concentration of the subject is significantly and specifically higher than one or more of the above reference standards, it can be used as a strong diagnostic basis for acute pancreatitis. Studies have confirmed that the elevation of AKG levels is particularly prominent in acute pancreatitis, thus effectively distinguishing it from healthy states or other inflammatory states; 2 Methods for assessing disease severity and monitoring: Dynamic tracking principle: By continuously testing at different time points during the patient's illness (e.g., the first, third, and seventh days after admission), the changing trend of AKG concentration in the body is dynamically tracked. If the AKG concentration shows a continuous decreasing trend, it usually indicates that the condition is improving or the treatment is effective. Conversely, if the concentration remains at a high level or further increases, it may indicate that the condition is serious or is deteriorating. Severity correlation principle: The absolute AKG concentration value of the patient at a specific time point after admission can be used to assess the severity of the disease. Studies have shown that there is a significant positive correlation between AKG concentration levels and serum amylase levels, a traditional biochemical indicator reflecting the degree of pancreatic damage. Therefore, higher AKG concentrations usually correspond to more severe pancreatic damage.

[0009] An application of α-ketoglutarate in the preparation of a drug for the treatment of acute pancreatitis.

[0010] Preferably, the drug is used to prevent or treat acute pancreatitis, as well as pancreatic tissue damage and distal organ (such as lung and kidney) damage caused by it. Animal experiments have shown that exogenous supplementation of α-ketoglutarate can significantly reduce pancreatic necrosis and edema caused by severe acute pancreatitis, and effectively alleviate serious complications such as acute lung injury and acute kidney injury.

[0011] Preferably, the administration form of the pharmaceutical composition includes, but is not limited to, a prodrug of α-ketoglutarate, a pharmaceutically acceptable salt, ester, or a targeted release formulation. The prodrug is a drug that can release α-ketoglutarate in vivo through metabolism or chemical decomposition. The targeted release formulation includes a carrier that covalently or non-covalently binds α-ketoglutarate, and the carrier includes cement hydrogel, oligosaccharide, or pectin carbohydrate.

[0012] Preferably, it also includes the use of α-ketoglutarate or a pharmaceutically acceptable salt thereof in the preparation of products for the diagnosis and / or auxiliary diagnosis of acute pancreatitis, including early screening, severity assessment or prognosis of acute pancreatitis.

[0013] Preferably, the use of α-ketoglutarate or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the prevention and / or treatment of acute pancreatitis, wherein the medicament is used to reduce serum amylase and / or lipase levels and to inhibit inflammatory responses in pancreatic tissue, and the inhibition of inflammatory responses includes reducing the levels of one or more of tumor necrosis factor-α, interleukin-1β and interleukin-6, and the medicament is in the form of an injection, enteric-coated tablet, capsule or tablet.

[0014] Preferably, the kit also includes a diagnostic kit for acute pancreatitis, comprising reagents for detecting α-ketoglutarate levels in a biological sample, wherein the biological sample is blood, serum, or plasma.

[0015] An acute pancreatitis animal model was established using taurine and lipopolysaccharide to verify the efficacy of exogenous supplementation of α-ketoglutarate. The results showed that oral supplementation of α-ketoglutarate significantly reduced pancreatic tissue pathological damage in the model mice and decreased the levels of amylase, lipase, and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in serum.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0017] This invention provides novel diagnostic and monitoring biomarkers: For the first time, this invention reveals the specific accumulation of endogenous α-ketoglutarate levels in the serum of patients with acute pancreatitis, and its levels are significantly positively correlated with disease severity indicators (such as amylase and white blood cell count). This provides a simple and effective serum biomarker for the early and accurate diagnosis and monitoring of acute pancreatitis, and offers a new, highly targeted treatment strategy: This invention provides a novel treatment regimen targeting the core pathogenesis of acute pancreatitis—energy metabolism disorder and mitochondrial damage—by supplementing exogenous α-ketoglutarate, which can directly "correct" this pathological state. It is highly targeted, theoretically sound, has significant therapeutic effects, and broad application prospects: Animal experiments have demonstrated that the α-ketoglutarate intervention regimen provided by this invention can not only effectively reduce pancreatic damage itself, but also significantly alleviate multi-organ complications such as acute lung injury and acute kidney injury, showing strong therapeutic potential. Since α-ketoglutarate is an endogenous metabolite, it has good safety, providing broad prospects for its clinical translation and application. Attached Figure Description

[0018] Figure 1 The clinical diagnostic value and related pathological manifestations of α-ketoglutarate (AKG) in acute pancreatitis (AP);

[0019] Figure 2 Macroscopic therapeutic effect of exogenous AKG supplementation on mice with severe acute pancreatitis (SAP);

[0020] Figure 3 One of the core mechanisms by which AKG exerts its therapeutic effect lies in the comprehensive repair of mitochondrial dysfunction.

[0021] Figure 4 Another key mechanism by which AKG exerts its therapeutic effect lies in activating the cell's endogenous protective signaling pathway. Detailed Implementation

[0022] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0023] In one specific embodiment of the invention, α-ketoglutarate was administered to mice via drinking water at an effective concentration of 0.5% (weight / volume). Based on this effective concentration, it is reasonable to expect that the effective concentration of α-ketoglutarate in the drug delivery composition for mammals (including humans) can be adjusted within a range. For example, in oral liquid formulations, its weight / volume percentage can be in the range of 0.1% to 5.0%, preferably 0.3% to 1.0%. Of course, the specific dosage and concentration need to be adjusted according to the patient's specific condition (such as weight, severity of illness) and the selected dosage form.

[0024] Example 1: Clinical validation of α-ketoglutarate as a biomarker for the diagnosis and monitoring of acute pancreatitis

[0025] To verify the potential of α-ketoglutarate (AKG) as a biomarker for acute pancreatitis (AP), this invention conducted a clinical study. The study prospectively enrolled 9 patients with acute pancreatitis, 10 patients with acute cholecystitis (as the inflammation control group), and 9 healthy volunteers (as the healthy control group). All subjects signed informed consent forms, and the study protocol was approved by the ethics committee. Peripheral blood samples were collected from all subjects, and serum was obtained after centrifugation and stored at -80°C until analysis by gas chromatography-mass spectrometry (GC-MS).

[0026]

[0027] Table 1: Comparison of baseline data and serum AKG and amylase levels among subjects in each group

[0028] As attached Figure 1 As shown, the study results confirm the clinical application value of AKG: diagnostic specificity ( Figure 1 A): Compared with healthy controls and acute cholecystitis controls, serum AKG levels were significantly and specifically elevated in patients with acute pancreatitis, indicating that AKG can serve as an effective biomarker to differentiate acute pancreatitis from other abdominal inflammations, and has potential for disease monitoring. Figure 1 B): Dynamic monitoring of serum samples from patients with acute pancreatitis on days 1, 3, and 7 after admission revealed that AKG levels dynamically changed with disease progression. This demonstrates that AKG can be used to monitor disease development and assess treatment response, and its correlation with disease severity is significant. Figure 1 D): Spearman correlation analysis showed that the level of AKG in the patient's serum was significantly positively correlated with the level of serum amylase (AMS), a classic indicator of pancreatic injury (correlation coefficient r = 0.51, p < 0.01), indicating that the concentration of AKG can reflect the severity of acute pancreatitis.

[0029] Example 2: The therapeutic effect of exogenous AKG supplementation on severe acute pancreatitis (SAP)

[0030] This invention uses intraperitoneal injection of lindane and lipopolysaccharide (LPS) to construct a severe acute pancreatitis (SAP) model in C57BL / 6J mice to verify the therapeutic effect of exogenous AKG supplementation. Thirty-two male mice were randomly divided into four groups (n=8): 1) healthy control group (HC); 2) AKG control group; 3) SAP model group; 4) SAP+AKG treatment group. The AKG control group and the SAP+AKG treatment group were allowed free access to an aqueous solution containing 0.5% AKG for 7 days before modeling. The mice were sacrificed 12 hours after modeling, and samples were collected for analysis.

[0031] Histopathological evaluation: as attached Figure 1 As shown in Figure C, the H&E staining results clearly demonstrate that the pancreatic tissue of the SAP model group mice exhibited extensive acinar necrosis, tissue edema, and inflammatory cell infiltration, as shown in the attached figure. Figure 2 As shown in Figure A, after AKG pre-intervention, the macroscopic morphology (necrosis, edema) of the pancreas in the SAP+AKG treatment group was greatly improved. Biochemical indicators were assessed as follows: (see attached figure). Figure 2 As shown in B and 2C, compared with the sharply elevated serum amylase and lipase levels in the SAP model group, both of these core indicators were significantly reduced in the SAP+AKG treatment group, indicating that pancreatic injury was effectively alleviated. Systemic inflammation assessment: see attached. Figure 2 As shown in D, 2E, and 2F, ELISA results indicate that AKG intervention significantly inhibited the release of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the serum of SAP model mice, effectively controlling excessive systemic inflammation caused by pancreatitis.

[0032] Example 3: AKG exerts its therapeutic effect by comprehensively repairing mitochondrial dysfunction.

[0033] To elucidate the core mechanism by which AKG exerts its therapeutic effect, this invention systematically evaluated the pancreatic tissue of mice in Example 2, as shown in the attached figure. Figure 3 As shown, AKG can comprehensively reshape cellular bioenergetics: at the ultrastructural level ( Figure 3 (A, 3B) Transmission electron microscopy revealed severe damage to pancreatic cell mitochondria in the SAP group, characterized by morphological swelling and loss of internal cristae. In contrast, the mitochondrial morphology in the AKG intervention group was significantly protected, with relatively intact structure and a significantly reduced damage score, indicating improved energy production function. Figure 3 C), quantitative results from the ATP assay kit showed that SAP led to a significant decrease in ATP content in pancreatic tissue, while AKG intervention effectively reversed this phenomenon, significantly restoring tissue ATP levels at the molecular functional level. Figure 3D, 3E) Western blotting was used to detect key proteins of each complex in the mitochondrial respiratory chain (MRC). The results showed that the protein expression levels of complex I (NDUFS3), complex III (UQCRC1), complex IV (MT-CO1), and complex V (ATP5A) were significantly downregulated in the SAP group, while AKG intervention significantly upregulated the expression of these key proteins, thereby restoring the integrity of the mitochondrial respiratory chain.

[0034] Example 4: AKG enhances cellular resistance by activating endogenous protective signaling pathways.

[0035] To further investigate the upstream signaling pathway regulated by AKG, this invention performed signaling pathway protein detection on the pancreatic tissue of the mice in Example 2, as shown in the attached figure. Figure 4 As shown, AKG can synergistically activate two major protective pathways: reactivating the AMPK energy sensing pathway ( Figure 4 A, 4B): Western blot analysis showed that under SAP conditions, the phosphorylation (activation) level of the cellular core energy sensor AMPK was severely suppressed. AKG intervention effectively restored the p-AMPK / AMPK ratio, indicating that AKG reactivated this key energy homeostasis regulation pathway and enhanced Nrf2-mediated antioxidant defense. Figure 4 C, 4D): AKG also significantly reversed the downregulation of expression of key proteins in the Nrf2 antioxidant pathway (Nrf2, SOD1, SOD2, HO-1, etc.) induced by SAP, thereby enhancing the endogenous antioxidant capacity of cells to combat oxidative stress damage during the AP process.

[0036] Example 5: Preparation of the pharmaceutical composition

[0037] 1. Preparation of AKG oral tablets:

[0038] Prescription: 500g sodium α-ketoglutarate, 150g microcrystalline cellulose, 30g croscarmellose sodium, 5g magnesium stearate.

[0039] Preparation method: The above raw and auxiliary materials are sieved, mixed evenly, and then made into tablets containing 250mg of AKG (calculated as acid) per tablet using a dry compression process.

[0040] Example 6: Therapeutic effect of AKG on a mouse model of acute pancreatitis induced by taurine.

[0041] 1. Animal Model Establishment and Grouping: Healthy male C57BL / 6 mice were randomly divided into four groups: normal control group, AKG group, AKG+SAP treatment group, and SAP group. An acute pancreatitis model was induced by multiple intraperitoneal injections of cerulein. The AKG treatment group received an appropriate dose of AKG solution via intraperitoneal injection immediately after the first cerulein injection.

[0042] 2. Indicator Testing:

[0043] • Serological testing: After the modeling is completed, blood is collected to separate serum and the activities of amylase and lipase are tested.

[0044] • Pathological examination: Pancreatic tissue was taken, fixed in formalin, embedded in paraffin, sectioned, stained with H&E, and histopathological changes were observed and pathological scores were made.

[0045] • Inflammatory factor detection: The levels of TNF-α and IL-6 in serum were detected using the ELISA method.

[0046] 3. Results:

[0047] Compared with the model group, serum amylase and lipase activities were significantly reduced in the AKG treatment group (especially the high-dose group) (P<0.01).

[0048] Pathological results showed that the pancreatic tissue pathological score of mice in the AKG treatment group was significantly lower than that in the model group, and the degree of pancreatic edema, inflammation, and necrosis was significantly suppressed (see [link to article]). Figure 1 ).

[0049] • Serum TNF-α and IL-6 levels in the AKG treatment group were also significantly lower than those in the model group (P<0.05).

[0050] The above results indicate that AKG has a significant therapeutic effect on taeniacin-induced acute pancreatitis.

[0051] in conclusion

[0052] This invention demonstrates through in vivo experiments that α-ketoglutarate can effectively treat and prevent acute pancreatitis, reducing pathological damage to pancreatic tissue and systemic inflammatory response. Therefore, AKG can be used to prepare safe and effective drugs for the treatment of acute pancreatitis.

[0053] Figure 1 Figure A shows a comparison of AKG levels in clinical serum samples. The results indicate that, compared with the healthy control group and the acute cholecystitis control group, patients with acute pancreatitis showed a significant and specific increase in serum AKG levels. Figure 1B is a graph showing the dynamic changes in serum AKG levels in patients with acute pancreatitis during the course of the disease (days 1, 3, and 7 after admission), demonstrating the trend of its level changes with the course of the disease and proving its potential for disease monitoring. Figure 1 C is a histopathological (H&E stained) section of pancreatic tissue from a mouse model of acute pancreatitis, showing the typical damage characteristics of pancreatic tissue in the disease state. Figure 1 D is the Spearman correlation analysis plot, which shows a significant positive correlation between serum AKG (α-ketoglutaric acid) levels and serum amylase levels, indicating that AKG concentration can reflect the severity of the disease. Figure 2 A shows the macroscopic morphology of the pancreas in mice from each experimental group, visually demonstrating that AKG treatment significantly reduced pancreatic tissue necrosis and edema induced by SAP. Figure 2 B and Figure 2 C represents the quantitative analysis of serum amylase and lipase, respectively, which, from a biochemical perspective, confirm that AKG can effectively reduce the core indicators of pancreatic damage. Figure 2 D, 2E, and 2F represent the serum levels of key pro-inflammatory cytokines IL-1β, IL-6, and TNF-α, respectively, confirming that AKG can significantly inhibit the systemic inflammatory response induced by SAP. Figure 3 Image A is a transmission electron microscope image of the ultrastructure of pancreatic mitochondria, demonstrating that AKG can significantly improve the morphological damage of mitochondria, including swelling and cristae breakage. Figure 3 B is a damage scoring map based on mitochondrial morphology, which quantifies the protective effect of AKG on mitochondrial structure. Figure 3 C is a quantitative analysis of ATP content in pancreatic tissue, confirming that AKG can restore mitochondrial energy production function. Figure 3 D and Figure 3 E represents the Western blotting and quantitative analysis of key proteins in the mitochondrial respiratory chain, respectively. This reveals at the molecular level that AKG can upregulate core functional proteins that are downregulated by SAP, thus restoring the integrity of the mitochondrial respiratory chain. Figure 4 A and Figure 4 B represents the Western blotting and quantitative analysis of the AMPK signaling pathway, confirming that AKG can reactivate the AMPK core energy sensor, which is suppressed in the SAP state. Figure 4 C and Figure 4 D represents the Western blotting and quantitative analysis of the Nrf2 antioxidant pathway, confirming that AKG can reverse the downregulation of key proteins in the Nrf2 pathway caused by SAP, thereby enhancing the cell's endogenous antioxidant defense capabilities.

[0054] Pharmacological studies have shown that exogenous α-ketoglutarate supplementation exerts its powerful therapeutic effect primarily by synergistically regulating two core cellular pathways, comprehensively repairing mitochondrial dysfunction. One of the core pathological events in severe acute pancreatitis (SAP) is the collapse of cellular energy metabolism and mitochondrial dysfunction. This invention demonstrates that α-ketoglutarate can comprehensively repair mitochondrial damage caused by SAP, including repairing swollen and broken ultrastructures of mitochondria, restoring intracellular ATP production, and significantly upregulating the expression levels of key proteins in the mitochondrial respiratory chain (such as complexes I, II, III, IV, and V), thereby reshaping cellular bioenergetic homeostasis and reactivating key protective signaling pathways. This invention also reveals that in SAP, two key protective pathways within the cell are severely inhibited, and α-ketoglutarate intervention can reactivate the AMPK energy sensing pathway, effectively restoring the AMP-activated protein, a core cellular energy sensor. Phosphorylation activation of AMPK restarts the regulatory center of cellular energy homeostasis and enhances Nrf2-mediated antioxidant defense: it significantly reverses the downregulation of key proteins in the Nrf2 antioxidant pathway (such as Nrf2, SOD1, SOD2, HO-1) induced by SAP, thereby enhancing the cell's endogenous antioxidant capacity to combat oxidative stress damage during AP. Previous studies of this invention have found that, compared with inflammations such as acute cholecystitis, AKG is specifically highly expressed in acute pancreatitis and is significantly correlated with serum amylase (R=0.51, P=0.0062). As the condition improves, AKG expression returns to normal levels. Therefore, AKG has the potential to serve as a biomarker for diagnosing and monitoring acute pancreatitis. Previous studies of this invention have found that feeding AKG to mice with acute pancreatitis can alleviate acute pancreatitis. In summary, AKG can be a way to treat pancreatitis.

[0055] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. The application of α-ketoglutarate in the preparation of a diagnostic reagent for diagnosing acute pancreatitis, characterized in that: The diagnosis of acute pancreatitis is achieved by detecting the concentration of α-ketoglutarate in the serum or plasma of the tested subject. Acute pancreatitis includes, but is not limited to, acute pancreatitis induced by cholelithiasis, hyperlipidemia, alcohol, drugs, or surgical trauma. Pharmaceutically acceptable salts of α-ketoglutarate include its sodium, potassium, calcium, or magnesium salts. The dosage form of the pharmaceutical composition is an oral or injectable formulation. Oral formulations include tablets, capsules, granules, and oral liquids; injectable formulations include injection solutions and sterile powders for injection.

2. The application according to claim 1 further provides the application of α-ketoglutarate in the preparation of diagnostic reagents for monitoring acute pancreatitis, characterized in that: By dynamically detecting changes in the concentration of α-ketoglutarate in the patient's serum or plasma, real-time monitoring of the patient's condition can be achieved.

3. An application according to claim 2, characterized in that: The specific principles and methods of judgment are explained in detail below:

1. Judgment method in diagnosis: Comparison principle: The core of diagnosis lies in comparing the concentration of α-ketoglutarate in the serum or plasma of the person being tested with one or more preset reference standards. The reference standards include: 1) the baseline level of AKG (α-ketoglutarate) concentration obtained from statistics of healthy people; 2) the AKG concentration level from a group of patients with other abdominal emergencies without pancreatitis and similar clinical symptoms. Diagnostic basis: When the AKG concentration of the person being tested is significantly and specifically higher than one or more of the above reference standards, it can be used as a strong diagnostic basis for having acute pancreatitis.

2. Judgment method in disease monitoring and severity assessment: Dynamic tracking principle: By continuously testing at different time points in the course of the patient's disease, the trend of changes in the AKG concentration in the body is dynamically tracked. If the AKG concentration shows a continuous downward trend, it usually indicates that the condition is improving or the treatment measures are effective. Conversely, if the concentration remains at a high level or further increases, it may indicate that the condition is serious or is deteriorating. Severity correlation principle: The absolute AKG concentration value of the patient at a specific time point after admission can be used to assess the severity of the disease.

4. An application of α-ketoglutarate in the preparation of a drug for the treatment of acute pancreatitis.

5. The application according to claim 4, characterized in that: The drug is used to prevent or treat acute pancreatitis, as well as pancreatic tissue damage and distal organ damage caused by it.

6. The application according to claim 4, characterized in that: The administration forms of the pharmaceutical composition include, but are not limited to, prodrugs of α-ketoglutarate, pharmaceutically acceptable salts, esters, or targeted-release formulations. The prodrug is a drug that can release α-ketoglutarate in vivo through metabolism or chemical decomposition. The targeted-release formulation includes a carrier that covalently or non-covalently binds α-ketoglutarate, and the carrier includes cement hydrogels, oligosaccharides, or pectin carbohydrates.

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