白虎二地汤改善2型糖尿病大鼠胰岛素抵抗分子机制的研究

The Molecular Mechanism of Baihu Erdi Decoction in The Improvement of Insulin Resistance in Type 2 Diabetic Rats

目的研究白虎二地汤对实验性2型糖尿病(T2DM)胰岛素抵抗大鼠炎症信号通路的影响,并探讨其机制。方法采用高糖高脂饲料喂养联合低剂量链脲佐菌素(STZ)腹腔注射建立T2DM胰岛素抵抗大鼠模型,将大鼠分为正常对照组、模型组、罗格列酮组、白虎二地汤高、低剂量组。连续给药6周后,观察其空腹血糖(FBG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、肿瘤坏死因子?α(TNF?α)、白介素-6(IL-6)的变化,采用Western blot法检测大鼠骨骼肌组织IRS-1、p-IRS-1和PI3Kp85蛋白的表达。结果白虎二地汤高剂量组可明显降低2型糖尿病大鼠FBG、FINS、HOMA-IR、TNF?α、IL-6(P<0.05),使骨骼肌组织IRS-1和p-IRS-1蛋白表达量降低,PI3Kp85蛋白的表达量升高。结论白虎二地汤可以改善STZ诱导的T2DM胰岛素抵抗大鼠炎症反应,减轻胰岛素抵抗。其可能的机制是通过炎症信号通路,减轻炎症反应,提高肌肉组织PI3K蛋白的表达,从而减弱外周胰岛素抵抗。

OBJECTIVE To explore the influence of Baihu Erdi decoction in inflammatory signaling pathways of experimen- tal type 2 diabetes mellitus （T2DM） rats with insulin resistance and how did these produce. METHODS T2DM insulin resist- ance rats were established by feeding with high-sucrose-fat diet for 8 weeks followed with streptozotocin （STZ） （30 mg/kg, i. p）. Rats were randomly divided into normal and diabetic group. After modeling, diabetic group were randomly divided into un- treated diabetic group, rosiglitazone group, and two Chinese medicine groups with different doses of Baihu Erdi decoction. Af- ter 6 weeks intervention, indicators as fasting blood glucose （FBG）, fasting insulin （FINS）, homeostasis model assessment-in- sulin resistance （HOMA-IR）, interleukin-6 （IL-6）, tumor necrosis factor α （TNF-α were detected from serum, insulin recep- tor substrate 1 （IRS-1）, anti-phospho-IRS-1 （p-IRS-1） and the eighty-five protein of phosphatidyl inositol 3-kinase were detec- ted from skeletal muscle organization by using western blots. RESULTS FBG, FINS, HOMA-IR, IL-6, TNF-α, as well as the expression of IRS-1 and p-IRS-1 proteins were significantly decreased in high dose Baihu Erdi decoction group （P〈0.05）, while the expression of PI3Kp85 was increased （P〈0.05）. CONCLUSION Baihu Erdi decoction supplementation could im prove inflammatory reaction and alleviate insulin resistance of STZ induced type 2 diabetic rats. The possible mechanism is Baihu Erdi decoction alleviates inflammatory reaction and improves expression of PI3K in muscle tissue by inflammatory signa- ling conduction, and thus enhances insulin resistance of target tissues.