盐酸二甲双胍联合清痰化瘀饮对链脲佐菌素和高脂饮食诱导的大鼠血脂和胰岛素抵抗的影响

Effect of metformin hydrochloride combined with Qingtan Huayu decoction on blood lipid and insulin resistance in rats induced by streptozotocin and high fat diet

目的探究盐酸二甲双胍联合清痰化瘀饮对大鼠血脂和胰岛素抵抗的影响。方法将SD大鼠随机分为对照组、模型组、盐酸二甲双胍组、清痰化瘀饮组、盐酸二甲双胍+清痰化瘀饮组,每组15只。通过尾静脉注射小剂量链脲佐菌素(STZ,15 mg/kg)和喂养高脂饲料建立胰岛素抵抗大鼠模型。然后分别对大鼠灌胃给予盐酸二甲双胍160 mg/(kg·d)或/和清痰化瘀饮500 mg/(kg·d),共治疗8周。治疗结束后,分别检测各组大鼠的生化指标空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、胰岛素(INS)和瘦素,氧化应激指标超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA),以及炎症因子肿瘤坏死因子-α(TNF-α)和白细胞介素(IL-1和IL-6)水平。通过苏木精和伊红(HE)染色评价胰腺组织形态。蛋白质印迹法检测胰腺组织中葡萄糖转运蛋白(GLUT-4)和胰岛素受体底物-1(IRS-1)的表达。结果与对照组比较,模型组FPG、TC、TG、LDL、INS、瘦素、MDA、TNF-α、IL-1和IL-6水平升高(P<0.05),HDL、SOD和GSH-Px水平降低(P<0.05),胰腺组织GLUT-4和IRS-1蛋白表达水平降低(P<0.05)。建模后,模型大鼠胰岛结构混乱,边界不清晰,细胞发生固缩和空泡化,脂肪浸润明显,证明建模成功。与模型组比较,盐酸二甲双胍组或清痰化瘀饮组FPG、TC、TG、LDL、INS、瘦素、MDA、TNF-α、IL-1和IL-6水平降低(P<0.05),HDL、SOD和GSH-Px水平升高(P<0.05),胰腺组织GLUT-4和IRS-1蛋白表达水平升高(P<0.05),胰岛形态和结构明显改善。与清痰化瘀饮组比较,盐酸二甲双胍+清痰化瘀饮组大鼠的空腹血糖水平降低(P<0.05)。与盐酸二甲双胍组或清痰化瘀饮组比较,盐酸二甲双胍+清痰化瘀饮组大鼠血清TC、TG、LDL、INS、瘦素、MDA、TNF-α、IL-1和IL-6水平降低(P<0.05),HDL、SOD和GSH-Px水平升高(P<0.05),胰腺组织GLUT-4和IRS-1蛋白表达水平升高(P<0.05),胰岛形态和结构明显改善。结论盐酸二甲双胍联合清痰化瘀饮对STZ和高脂饮食诱导的大鼠血脂异常和胰岛素抵抗的缓解作用优于单药。

Objective To explore the effect of metformin hydrochloride combined with Qingtan Huayu decoction on blood lipid and insulin resistance.Methods SD rats were randomly divided into control group,model group,metformin hydrochloride group,Qingtan Huayu decoction group,metformin hydrochloride+Qingtan Huayu decoction group,with 15 rats in each group.The rat model of insulin resis-tance was established by tail vein injection of low-dose streptozotocin(STZ,15 mg/kg)and feeding of high-fat diet.Then rats were given metformin hydrochloride[160 mg/(kg·d)]or/and Qingtan Huayu decoction[500 mg/(kg·d)]by gavage for 8 weeks.After treatment,the biochemical indicators fasting blood glucose(FPG),total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL),high density lipoprotein(HDL),insulin(INS)and leptin,oxidative stress indicators superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and malondialdehyde(MDA),and inflammatory factors tumor necrosis factor-α(TNF-α)and interleukins(IL-1 and IL-6)were measured.Morphological changes of pancreatic tissue were observed by HE staining.Western blot was used to detect the expression of glucose transporter(GLUT-4)and insulin receptor substrate-1(IRS-1)in pancreatic tissue.Results Compared with control group,the levels of FPG,TC,TG,LDL,INS,leptin,MDA,TNF-α,IL-1 and IL-6 were increased in model group(P<0.05),the levels of HDL,SOD and GSH-Px were decreased(P<0.05),and GLUT-4 and IRS-1 protein expression levels were decreased in pancreatic tissue(P<0.05).After modeling,the islet structure of the model rat was chaotic,the boundary was not clear,the cells were pyknotic and vacuolated,and the fat infiltration was obvious,which proved that the modeling was successful.Compared with model group,the levels of FPG,TC,TG,LDL,INS,leptin,MDA,TNF-α,IL-1 and IL-6 in metformin hydrochloride group or Qingtan Huayu decoction group were decreased(P<0.05),HDL,SOD and GSH-Px levels were increased(P<0.05),GLUT-4 and IRS-1 protein expression levels were increased in pancreatic tissue(P<0.05),and the morphology and the structure of pancreatic islets were significantly improved.Compared with Qingtan Huayu decoction group,the rats in metformin hydrochloride+Qingtan Huayu decoction group had lower fasting blood glucose(P<0.05).Compared with metformin hydrochloride group or Qingtan Huayu decoction group,the serum levels of TC,TG,LDL,INS,leptin,MDA,TNF-α,IL-1 and IL-6 in hydrochloride+Qingtan Huayu decoction group were decreased,the levels of HDL,SOD and GSH-Px were increased(P<0.05),the protein expression levels of GLUT-4 and IRS-1 in pancreatic tissue were increased(P<0.05),and the morphology and the structure of pancreatic islets were significantly improved.Conclusion The effect of metformin hydrochloride combined with Qingtan Huayu decoction on dyslipidemia and insulin resistance in rats induced by STZ and high-fat diet is better than that of single drug.