高活性小牛血去蛋白提取物对糖尿病大鼠肾损伤的保护作用

摘要

Objective:To observe the protective effect of deproteinized extract of calf blood (DECB) on the kidney injury of the diabetic rats, and to discuss its mechanism preliminarily.Methods:The male Wistar rats were intraperitoneally injected with STZ (65 mg·kg-1) to establish the diabetes models, then the model rats were randomly divided into model (M)group, and metformin (MMet, 105 mg·kg-1) group , low dose of combined administration (ML,105 mg·k-1 metformin+94.5 mg·kg-1 ,DECB) group, medium dose of combined administration(MM, 105 mg·kg-1 metformin+ 189 mg·kg-1 DECB) group, high dose of combined administration(MH, 105 mg·kg-1 metformin +378 mg·kg-1,DECB) group, another ten Wistar rats were selected as normal control(NC)group.The rats were intragastrically administed with metformin and intraperitoneally injected with DECB, once a day, total of 8 weeks.The rats in NC group and M group were given normal saline solution.The weights and blood glucose levels of the rats in various groups were determined;the levels of serum high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), blood urea nitrogen (BUN), urinary albumin (UAlb), urine creatinine (UCR), serum creatinine (SCr), total cholesterol (TC), triglyceride (TG), uric acid (UA), glutathione (GSH), and malondialdehyde (MDA) were detected;the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined.The pathological changes of kidney tissue of the rats in various groups were detected by HE staining.Results:Compared with NC group, the weight of the rats in M group was reduced(P<0.05),and the levels of blood glucose,UAlb,UCr,SCr,UA,BUN,LDL-C,TC,TG,and MDA were increased(P<0.05);the levels of HDL-C and GSH were obviously reduced(P<0.05),and the activities of SOD adn GSH-Px were obviously reduced(P<0.05).Compared with M group,the weights of the rats in MM and MH groups were increased (P<0.05), and the levels of blood glucose,UAlb,UCr,SCr,UA,BUN,LDL-C,TC,TG, and MDA were decreased (P< 0.05);the levels of HDL-C and GSH were increased (P<0.05),and the activities of SOD and GSH-Px were increased (P<0.05).The pathological observation of kidney tissue showed that the rats in M group had obvios kidney tissue lesions with glomerular congestion and renal tubular edema compared with NC group;compared with M group,the pathological changes of the kidney tissue of the rats in drug administration groups were significantly improved, the renal tubular vacuoles were reduced, and the interstitial hyperplasia was not obvious.Conclusion:DECB combined with metformin can reduce the blood glucose level, regulate blood lipid, improve the pathological changes of kidney tissue in the diabetic rats, reduce the renal damage, and enhance the antioxidant capacity of the body.%目的:观察小牛血去蛋白提取物(DECB)对糖尿病大鼠肾损伤的保护作用,并初步探讨其作用机制.方法: Wistar雄性大鼠腹腔注射STZ(65 mg·kg-1)建立糖尿病模型,将成模大鼠随机分为模型(M)组、二甲双胍(MMet,105 mg·kg-1)组、低剂量DECB联合给药(ML,105 mg·kg-1二甲双胍+94.5 mg·kg-1DECB)组、中剂量DECB联合给药(MM, 105 mg·kg-1二甲双胍 + 189 mg·kg-1DECB)组和高剂量联合给药(MH,105 mg·kg-1二甲双胍+378 mg·kg-1DECB)组(n=10),另取10只Wistar大鼠作为正常对照(NC)组(n=10).二甲双胍为经口灌胃给药,DECB为腹腔注射给药,每天1次,共给药8周,NC组和M组大鼠给予等体积的生理盐水.测定各组大鼠体质量、血糖水平,检测各组大鼠血清中高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、尿素氮(BUN)、尿微量白蛋白(UAlb)、尿肌酐(UCr)、血肌酐(SCr)、总胆固醇(TC)、甘油三酯(TG)、尿酸(UA)、谷胱甘肽(GSH)、丙二醛(MDA)水平和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性;HE染色观察各组大鼠肾脏组织病理形态学表现.结果:与NC组比较,M组大鼠体质量降低,空腹血糖、UAlb 、UCr、SCr、UA、BUN、LDL-C、TC、TG和MDA水平升高(P<0.05),HDL-C和GSH水平降低(P<0.05),SOD和GSH-Px活性降低(P<0.05).与M组比较,MM和MH组大鼠体质量升高(P<0.05),血糖、UAlb 、UCr、SCr、UA、BUN、LDL-C、TC、TG和MDA水平降低(P<0.05),HDL-C和GSH水平升高(P<0.05),SOD和GSH-Px活性升高(P<0.05).肾脏组织病理观察,与NC组比较,M组大鼠肾脏组织病变明显,肾小球充血,肾小管水肿;与M组比较,各给药组大鼠肾脏组织病变明显好转,肾小管空泡变性减轻,间质增生不明显.结论:DECB联合二甲双胍给药可降低糖尿病大鼠血糖,调节血脂,改善糖尿病大鼠肾组织病理学变化,减轻肾脏损伤,提高机体的抗氧化能力.