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目的探讨川芎嗪对链脲佐菌素(streptozocin,STZ)诱导2型糖尿病大鼠肾病的治疗作用及机制。方法 SD大鼠70只,随机分为正常组和模型组。除正常组外,其余大鼠均给予高脂-高糖饲料喂养4周,再给予链脲佐菌素(40 mg·kg-1,ip),72 h后测定空腹血糖,将血糖值大于16.67 mmol·L-1的大鼠随机分为4组:模型组,二甲双胍组(250 mg·kg-1),川芎嗪低剂量组(80 mg·kg-1)和高剂量组(160 mg·kg-1),连续给药8周。正常对照组和模型组大鼠均灌胃给予等量蒸馏水。实验结束时,测定大鼠胰岛素(Ins)、血糖(FSG)和血脂含量及胰岛素抵抗指数(HOMA-IRI);测定大鼠尿量、尿蛋白、血尿素氮和血肌酐含量;测定大鼠肾素-血管紧张素(AngⅡ)、P选择素(P-selectin)含量、肾组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。光镜下观察肾脏病理学变化。结果与模型组比较,二甲双胍和高、低剂量川芎嗪给药8周后,均能明显降低大鼠动态空腹血糖(P<0.05),动态尿蛋白总排出量显著性降低(P<0.01,P<0.05);二甲双胍组和高、低剂量川芎嗪组,均能明显降低大鼠血清胰岛素,血糖、TC、LDL-C、TG、FFAs、BUN、Cr、胰岛素抵抗指数和血脂、肾组织丙二醛、血管紧张素Ⅱ(AngⅡ)及P-选择素含量,明显提高高密度脂蛋白-胆固醇(HDL-C)水平、肾组织氧化亚氮(NO)含量和一氧化氮合酶(NOS)及超氧化物歧化酶的活性(P<0.01或P<0.05)。肾脏组织病理性损伤明显减轻。结论川芎嗪对链脲佐菌素诱导2型糖尿病大鼠肾病具有保护作用,其机制可能与干预高糖血症、血脂代谢障碍和氧化应激反应,拮抗胰岛素抵抗,以及下调肾素-血管紧张素和P-选择素作用有关。
Objective To investigate the therapeutic effect and mechanism of ligustrazine on nephropathy induced by streptozocin (STZ) in type 2 diabetic rats. Methods Seventy SD rats were randomly divided into normal group and model group. Except the normal group, the other rats were fed with high-fat and high-sugar diet for 4 weeks, then given streptozotocin (40 mg · kg-1, ip), fasting blood glucose was measured 72 h later, blood glucose was greater than 16.67 rats were randomly divided into 4 groups: model group, metformin group (250 mg · kg -1), ligustrazine low dose group (80 mg · kg -1) and high dose group (160 mg · kg -1) -1) for 8 weeks. The normal control group and model group rats were intragastrically given the same amount of distilled water. At the end of the experiment, rats’ insulin, blood glucose (FSG), blood lipid and insulin resistance index (HOMA-IRI) were measured. Urinary output, urine protein, blood urea nitrogen and serum creatinine were measured. Ang Ⅱ, P-selectin, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in renal tissue. The pathological changes of kidney were observed under light microscope. Results Compared with the model group, both metformin and high and low doses of ligustrazine significantly decreased the fasting blood glucose (P <0.05) and the total urinary protein excretion (P <0.01, P <0.05). Both metformin group and high-dose and low-dose ligustrazine groups could significantly reduce the serum insulin, blood glucose, TC, LDL-C, TG, FFAs, BUN, Cr, insulin resistance index and blood lipid, Aldehyde, angiotensin Ⅱ and P-selectin, and significantly increased the levels of high density lipoprotein-cholesterol (HDL-C), nitric oxide (NO) and nitric oxide synthase (NOS) Superoxide dismutase activity (P <0.01 or P <0.05). Pathological damage of kidney tissue was significantly reduced. Conclusion Tetramethylpyrazine has a protective effect on streptozotocin-induced nephropathy in type 2 diabetic rats. The mechanism may be related to the intervention of hyperglycemia, dyslipidemia and oxidative stress, antagonism of insulin resistance and down-regulation of renin-vascular tone Su and P-selectin role.