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目的研究吊竹梅水提物(AEZPS)对链脲佐菌素(STZ)所致糖尿病肾损伤小鼠的肾保护作用。方法采用尾静脉注射STZ建立糖尿病模型,然后按照体重随机分4组:模型组、大中小3个剂量实验组(吊竹梅提取物相当于生药40,20,10 g·kg~(-1)),每组10只。同时,另设10只健康小鼠作为空白组,模型组与空白组灌胃双蒸水(20 m L·kg~(-1))。灌胃给药28 d,取血。测定空腹血糖(FBG)、血尿素氮(BUN)、血肌酸酐(Scr)和血脂水平,取双肾称重,计算肾指数(肾重/体重)。以苏木精-伊红染色观察肾组织的病理变化。以免疫组化染色观察肾组织的Toll样受体4(TLR4)因子和核转录因子-κB(NF-κB)的表达情况。结果与空白组比较,模型组的空腹血糖、三酰甘油(TG)、总胆固醇(TC)、血尿素氮、血肌酸酐水平和肾指数分别为(28.01±3.94),(1.73±0.29),(3.16±0.39),(15.12±2.23)mmol·L~(-1)和(64.98±4.45)μmol·L~(-1)及(22.36±2.04)mg·g~(-1),明显升高;而高密度脂蛋白胆固醇(HDL-C)水平为(1.57±0.29)mmol·L~(-1),显著下降,差异均有统计学意义(均P<0.01)。与模型组相比,大剂量实验组的FBG、TG、TC、BUN、Scr和肾指数分别为(20.93±3.39),(1.52±0.26),(2.54±0.20),(12.57±1.43)mmol·L~(-1)和(57.36±8.99)μmol·L~(-1)及(19.32±3.68)mg·g~(-1),有明显下降;而HDL-C为(1.81±0.16)mmol·L~(-1),有明显地升高,差异均有统计学意义(P<0.01或P<0.05)。中剂量实验组的FBG、TG、TC和BUN分别为(21.81±4.89),(1.44±0.24),(2.60±0.38)和(13.46±1.73)mmol·L~(-1),明显下降,差异均有统计学意义(P<0.01或P<0.05)。给药后,肾的病理学变化得到改善,肾组织TLR4和NF-κB的表达明显下调。结论 AEZPS可能通过降低血糖,调节血脂、改善肾功能和下调肾组织TLR4和NF-κB的表达来保护糖尿病小鼠的肾。
Objective To study the renal protective effect of aqueous extract of Diazepam (AEZPS) on diabetic nephropathy induced by streptozotocin (STZ) in mice. Methods The model of STZ was established by injection of STZ into the tail vein. The rats were randomly divided into 4 groups according to the body weight: model group, Dazhong Xiao 3 experimental groups (40, 10, 10 g · kg -1) ), 10 in each group. At the same time, another 10 healthy mice were set as the blank group. The model group and the blank group were given distilled water (20 m L · kg -1). Gavage 28 d, take blood. The fasting blood glucose (FBG), blood urea nitrogen (BUN), blood creatinine (Scr) and blood lipid levels were measured. The kidneys were weighed and the renal index (renal weight / body weight) was calculated. The pathological changes of renal tissue were observed by hematoxylin-eosin staining. The expression of Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) in renal tissues were observed by immunohistochemistry. Results Compared with the blank group, fasting blood glucose, triglyceride (TG), total cholesterol (TC), blood urea nitrogen, serum creatinine and renal index were (28.01 ± 3.94) and (1.73 ± 0.29) (3.16 ± 0.39), (15.12 ± 2.23) mmol·L -1 and (64.98 ± 4.45) μmol·L -1 and (22.36 ± 2.04) mg · g -1, respectively, While the level of HDL-C was (1.57 ± 0.29) mmol·L -1, which was significantly lower (all P <0.01). Compared with the model group, FBG, TG, TC, BUN, Scr and renal index in the high dose group were (20.93 ± 3.39), (1.52 ± 0.26), (2.54 ± 0.20) and (12.57 ± 1.43) mmol · (-1) and (57.36 ± 8.99) μmol·L -1 and (19.32 ± 3.68) mg · g -1, respectively, while the HDL-C level was (1.81 ± 0.16) mmol·L -1 · L ~ (-1), which were significantly increased, the differences were statistically significant (P <0.01 or P <0.05). FBG, TG, TC and BUN in the middle dose group were (21.81 ± 4.89), (1.44 ± 0.24), (2.60 ± 0.38) and (13.46 ± 1.73) mmol·L -1, respectively, All were statistically significant (P <0.01 or P <0.05). Pathological changes of the kidneys were improved after administration, and the expressions of TLR4 and NF-κB in the kidney were significantly down-regulated. Conclusion AEZPS may protect the kidneys of diabetic mice by decreasing blood glucose, regulating blood fat, improving renal function and decreasing the expression of TLR4 and NF-κB in renal tissues.