茵陈苓桂剂对非酒精性脂肪性肝炎大鼠胰岛素抵抗的影响

Effect of Yinchen Linggui Prescription on insulin resistance in nonalcoholic steatohepatitis rats

目的:观察茵陈苓桂剂对非酒精性脂肪性肝炎(NASH)大鼠胰岛素抵抗的影响,探讨茵陈苓桂剂对NASH大鼠的作用机制。方法:将60只SPF级雄性SD大鼠适应性喂养7 d后,随机分成正常组(10只)和造模组(50只),正常组予以普通饲料喂养,造模组予以高脂饲料喂养8周;在造模组中随机取2只大鼠,确定造模成功后,再将造模组剩下的48只大鼠随机分为模型组(8只)、茵陈苓桂剂高剂量组(10只)、茵陈苓桂剂中剂量组(10只)、茵陈苓桂剂低剂量组(10只)和多烯磷脂酰胆碱组(10只);予对应灌胃药物给药4周。测定大鼠的体重和肝湿重以计算肝指数,测量大鼠空腹血清葡萄糖(GLU)含量和用ELISA测定胰岛素(INS)水平,来计算胰岛素抵抗指数(HOMA-IR)。用生化法检测大鼠丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆固醇(T-CHO)和甘油三酯(TG)含量;ELISA测定大鼠游离脂肪酸(FFA)、瘦素(LEP)、脂联素(APN)水平。结果:与正常组比较,模型组大鼠的肝指数、HOMA-IR及大鼠血清ALT、AST、T-CHO、TG、FFA水平显著增高(P<0.01),血清及肝组织匀浆LEP水平显著升高(P<0.01),APN水平显著降低(P<0.01)。与模型组比较,多烯磷脂酰胆碱组及茵陈苓桂剂各剂量组大鼠肝指数、HOMA-IR值及大鼠血清AST、T-CHO水平显著降低(P<0.01或P<0.05),血清APN水平显著升高(P<0.01或P<0.05);多烯磷脂酰胆碱组及茵陈苓桂剂高、中剂量组大鼠ALT、TG水平均显著性降低(P<0.01或P<0.05),肝组织匀浆APN水平显著升高(P<0.01);多烯磷脂酰胆碱组及茵陈苓桂剂高剂量组大鼠血清FFA水平显著降低(P<0.01)。在血清及肝组织匀浆LEP含量方面,多烯磷脂酰胆碱组大鼠与模型组比较显著降低(P<0.01或P<0.05);而茵陈苓桂剂对于NASH大鼠血清及肝组织匀浆LEP水平的影响差异无统计学意义(P>0.05)。结论:茵陈苓桂剂能够通过改善肝指数、HOMA-IR及ALT、AST、T-CHO、TG、FFA水平,调控血清及肝组织匀浆APN含量,降低胰岛素抵抗,而达到防治NASH的目的。

Objective: Observation of the effect of Yinchen Linggui Prescription on insulin resistance in rats with nonalcoholic steatohepatitis(NASH). To explore the mechanism of action of Yinchen Linggui prescription on NASH rats. Methods: After 60 SPF male SD rats were fed adaptively for 7 days, they were randomly divided into normal group(10) and model group(50). The normal group was fed with normal feed and the model was fed with high-fat feed for 8 weeks. Randomly take 2 rats in the model, and determine the success of the model, then randomly divide the remaining 48 rats in the model into the model group(8), Yinchen Linggui Prescription high-dose group(10), Yinchen Linggui Prescription medium-dose group(10), Yinchen Linggui Prescription low-dose group(10), and polyene phosphatidylcholine group(10);corresponding drugs were given for 4 weeks. The body mass and wet liver weight of the rats were measured to calculate the liver index. The fasting serum glucose(GLU) content of rats was measured and the insulin(INS) level was measured by ELISA to calculate the insulin resistance index(HOMA-IR). Biochemical methods were used to detect rats alanine aminotransferase(ALT), aspartate aminotransferase(AST), total cholesterol(T-CHO) and triglyceride(triglyceride, TG) content. ELISA measures the levels of free fatty acid(FFA), leptin(LEP) and adiponectin(APN) in rats. Results: Compared with the normal group, the liver index, HOMA-IR and serum ALT, AST, T-CHO, TG, and FFA levels of the model group were significantly increased(P<0.01), and the LEP level of serum and liver tissue homogenate was significantly Increased(P<0.01), APN level was significantly reduced(P<0.01). Compared with the model group, the liver index, HOMA-IR value and serum AST and T-CHO levels of rats in the polyene phosphatidylcholine group and Yinchen Linggui prescription each dose group were significantly reduced(P<0.01 or P<0.05), The serum APN level was significantly increased(P<0.01 or P<0.05);The levels of ALT and TG of rats in the polyene phosphatidylcholine group and Yinchen Linggui Prescription agent high and medium dose groups were significantly reduced(P<0.01 or P<0.05), and the APN level of liver tissue homogenate was significantly increased(P<0.01). The serum FFA level of rats in the polyene phosphatidylcholine group and the Yinchen Linggui Prescription agent high-dose group was significantly reduced(P<0.01). In terms of LEP content in serum and liver tissue homogenate, rats in the polyene phosphatidylcholine group were significantly lower than the model group(P<0.01 or P<0.05). The effect of Yinchen Linggui Prescription on the LEP levels of serum and liver tissue homogenates of NASH rats has not been found to be statistically significant(P>0.05). Conclusion: Yinchen Linggui Prescription can prevent and cure NASH by improving liver index, HOMA-IR and ALT, AST, T-CHO, TG, FFA levels, regulating APN content in serum and liver tissue homogenate, and reducing insulin resistance.