【摘要】 目的 探讨黄芪甲苷（AS-Ⅳ）对链脲佐菌素（STZ）诱导糖尿病肾病（DN）大鼠的作用机制。方法 选择SPF级雄性6周龄SD大鼠30只，随机取6只大鼠作为对照组，剩余24只大鼠按65 mg/kg腹腔注射STZ （溶于0.1 mol/L柠檬酸缓冲液，pH 4.4）制备DN模型，对照组腹腔注射等体积0.1 mol/L柠檬酸缓冲液，将模型大鼠随机分为模型组、AS-Ⅳ组、胰岛素（INS）组、AS-Ⅳ+INS组各6只，分别给予AS-Ⅳ 10 mg/kg、INS 5 U、AS-Ⅳ 10 mg/kg+INS 5 U灌胃，对照组和模型组灌胃等体积1%羧甲基纤维素钠溶液，1次/d，干预8周。对比各组血糖、体质量、尿蛋白、BUN、Scr、HbA1c，血清和肾组织一氧化氮（NO）水平，肾组织中内皮型一氧化氮合酶（eNOS）、磷酸化一氧化氮合成酶丝氨酸1177位点[peNOS(Ser1177)]和苏氨酸495位点[p-eNOS(Thr495)]蛋白表达。结果 与对照组比较，模型组血糖均升高（P<0.05）;AS-Ⅳ组、INS组、AS-Ⅳ+INS组从第8周开始血糖值均低于模型组（P<0.05）；但AS-Ⅳ组、INS组、AS-Ⅳ+INS组间血糖比较差异无统计学意义（P>0.05）。与对照组比较，所有造模大鼠体质量低（P<0.05），尿蛋白、BUN、Scr、HbA1c高（P<0.05）；与模型组比较，AS-Ⅳ组、INS组、AS-Ⅳ+INS组体质量高（P<0.05），尿蛋白、BUN、Scr、HbA1c低（P<0.05）；与INS组比较，AS-Ⅳ+INS组尿蛋白、Scr低（P<0.05）。与对照组比较，模型组血清和肾组织NO水平低（P<0.05）；与模型组比较，AS-Ⅳ组、INS组、AS-Ⅳ+INS组血清和肾组织NO水平高（P<0.05）；与INS组比较，AS-Ⅳ+INS组肾组织NO水平高（P<0.05）。与对照组比较，模型组肾组织中p-eNOS(Ser1177)蛋白表达低（P<0.01）；与模型组比较，AS-Ⅳ组、AS-Ⅳ+INS组肾组织中p-eNOS(Ser1177)蛋白表达高（P<0.01）。结论 黄芪甲苷可能通过eNOS/NO通路对STZ诱导DN大鼠发挥治疗，且作用位点可能在Ser1177。更多还原

【Abstract】 Objective To explore the protective mechanism of astragaloside Ⅳ(AS-Ⅳ) through endothelial nitric oxide synthase(eNOS)/nitric oxide(NO) pathway in kidney of diabetic rats. Methods Thirty SPF male SD rats aged 6 weeks were selected.Except of the control group(n=6), the remaining 24 rats were intraperitoneally injected with 65 mg/kg STZ(dissolved in 0. 1 mol/L citric acid buffer, pH 4. 4) to make DN model, while the control group was intraperitoneally injected with the same volume of 0. 1 mol/L citric acid buffer. The model rats were randomly divided into model group, AS-Ⅳ group, insulin(INS)group and AS-Ⅳ+INS group with 6 rats in each group. AS-Ⅳ 10 mg/kg, INS 5 U and AS-Ⅳ 10 mg/kg+INS 5 U were given by gavage respectively, and the control group and the model group were given the same volume of 1% sodium carboxymethyl cellulose solution once a day for 8 weeks. The blood sugar, body weight, urine protein, BUN, Scr, HbA1c, nitric oxide(NO) levels in serum and kidney, and the sites of endothelial nitric oxide synthase(eNOS), phosphorylated nitric oxide synthase serine 1 177[P-Enos(SER 1 177)] and threonine 495 [P-Enos(THR 495)] in kidney were compared. Results Compared with the control group, the blood sugar in the model group was increased(P<0. 05). The blood sugar levels in As-ⅳ group, INS group and As-ⅳ+INS group were lower than those in the model group from the 8th week(P<0. 05). However, there was no significant difference in blood glucose among As-ⅳ group, INS group and As-ⅳ+INS group(P>0. 05). Compared with the control group,the body weight of the model group was lower(P<0. 05), and the urine protein, BUN, Scr and HbA1c were higher(P<0. 05).Compared with the model group, AS-Ⅳ group, INS group and AS-Ⅳ+INS group had higher body mass(P<0. 05), but lower urine protein, BUN, Scr and HbA1c(P<0. 05). Compared with INS group, urinary protein and Scr in AS-ⅳ+INS group were lower(P<0. 05). Compared with the control group, the level of NO in serum and kidney tissue in the model group was lower(P<0. 05). Compared with the model group, AS-Ⅳ group, INS group and AS-Ⅳ+INS group had higher levels of NO in serum and kidney tissue(P<0. 05). Compared with INS group, the level of NO in renal tissue in AS-ⅳ+INS group was higher(P<0. 05).Compared with the control group, the expression of p-eNOS(Ser1177) protein in renal tissue of model group was lower(P<0. 01). Compared with the model group, the expression of p-eNOS(Ser1177) protein in renal tissue of As-Ⅳ group and As-Ⅳ+INS group was higher(P<0. 01). Conclusion Astragaloside Ⅳ may play a role in treating STZ-induced DN rats through eNOS/NO pathway, and the site of action may be Ser1177.更多还原