摘要
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(Ang Ⅱ)、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
Abstract
OBJECTIVE To investigate the therapeutic effects and mechanisms of tetramethylpyrazine (TMP)on streptozocin (STZ)-induced-nephropathy in type 2 diabetic rats. METHODS Seventy SD rats were divided into control group (n=14)and model group (n=56)at random. The model rats were fed on high fat and sugar diets for 4 weeks and then injected STZ 40 mg·kg-1. After 72 h, the fasting blood glucose (FBG)was measured. Rats with high FBG above 16.67 mmol·L-1 were randomly divided into four groups: model, metformin (Met, 250 mg·kg-1)and TMP (80,160 mg·kg-1)groups and continuously treated for 8 weeks, and both the control and model groups were given equal distilled water by intragastric administration. The levels of insulin (Ins), fasting serum glucose (FSG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), free fatty acids (FFAs), angiotensin II (Ang II)and P-selectin, blood urea nitrogen (BUN), creatinine(Cr), creatinine clearance rate (Ccr)in serum, contents of nitric oxide (NO)and activities of nitric oxide synthetase (NOS)in serum and renal tissues, content of malonaldehyde (MDA)and activity of superoxide dismutase (SOD)in renal tissues, and the insulin resistance index (HOMA-IRI)were measured at the end of the experiment. Besides, the urine volume and urinary protein were also determined. The nephridial tissues of the treated rats were observed under optical microscope. RESULTS Compared with model group, the dynamic FBG and total output of urinary protein were significantly decreased (P
关键词
川芎嗪 /
链脲佐菌素 /
糖尿病肾病 /
胰岛素抵抗 /
血管紧张素Ⅱ /
P-选择素
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Key words
tetramethylpyrazine /
diabetic nephropathy /
insulin resistance /
angiotensin Ⅱ /
P-selectin
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傅永锦,周艳,潘竞锵,张小牧,吕俊华.
川芎嗪对链脲佐菌素诱导2型糖尿病大鼠肾病的治疗作用及机制[J]. 中国药学杂志, 2012, 47(22): 1807-1812
FU Yong-jin, ZHOU Yan,PAN Jing-qiang, ZHANG Xiao-mu,Lv Jun-hua.
The rapeutic Effects and Mechanisms of Tetramethylpyrazine on Streptozocin-Induced-Nephropathy in Type 2 Diabetic Rats[J]. Chinese Pharmaceutical Journal, 2012, 47(22): 1807-1812
中图分类号:
R965
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参考文献
[1] ZHOU J S, KONG Y, SHENTU J Z,et al. Study on content variation of active ingredient between single and mixed decoction on ligusticum Chua-nxiong and angelic[J]. Chin Pharm J(中国药学杂志),2008,43(2):95-98.
[2] HUANG J Z. Clinical efficacy of ligustrazine hydrochloride injection in treating renal failure caused by diabetic nephropathy[J]. China Pract Med (中国实用医药),2010,5(12):44-45.
[3] ZHANG R, LI S M, YE S D, et al. Effect of pioglitazone on renal and MCP-l expression in Type2 diabetic rat[J]. Int J Pathol Clin Med (国际病理科学与临床杂志),2010,30(1):33-38.
[4] HU S H,ZHANG M X. The protective effect of baicalin on the kidney of STZ induced diabetic rats and its relation to VEGF[J]. Chin Hosp Pharm J (中国医院药学杂志), 2007,27(7):885-888.
[5] LU H E, JIAN C H, CHEN S F, et al. Hypoglycaemic effects of fermented mycelium of Paecilomyces farinosus (G30801)on high-fat fed rats with streptozotocin-induced diabetes[J]. Indian J Med Res, 2010,131(5):696-701.
[6] MADKOR H R, MANSOUR S W, RAMADAN G. Modulatory effects of garlic, ginger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-nicotinamide diabetic rats[J]. Br J Nutr, 2011,105(8):1210-1217.
[7] KOBAYASHI T, TAGUCHI K, NEMOTO S, et al. Activation of the PDK-1/Akt/eNOS pathway involved in aortic endothelial function differs between hyperinsulinemic and insulin-deficient diabetic rats[J].Am J Physiol Heart Circ Physiol, 2009,297(5):1767-1775.
[8] ARYA A, YADAV H N, SHARMA P L. Involvement of vascular endothelial nitric oxide synthase in development of experimental diabetic nephropathy in rats[J]. Mol Cell Biochem, 2011,354(1-2):57-66.
[9] FENG R E,ZHENG L Y,LV J H,et al.Effects of total glucosides of paeong on improving insulin sensitivity,lowering blood pressure and enhancing antioxidation in metabolic syn-drome-hypertensive rats[J].Chin J Clin Pharmacol Ther (中国临床药理学与治疗学),2010,15(2):154-159.
[10] WU W X,CHEN X Y,WANG Q Z,et al.Effectof telmisartan on expression of typeⅠinositol1, 4, 5-trisphos-phate receptor in kidney tissues of diabetic nephropathy rats[J].J Zhengzhou Univ (Med Sci)(郑州大学学报:医学版),2011,46(2):195-197.
[11] CHEN L L,LIU L Q.The effect of leflunomide on renal expression of P-selectin mRNA in diabetic rats[J].Chin J Lab Diagn(中国实验诊断学), 2010,14(5): 654-659.
[12] YANG L, SHAO W B, YAO G Y,et al. Ligustrazine injection for diabetic nephropathy:A systematic review[J]. Chin J Infor Tradit Chin Med (中国中医药信息杂志), 2011,18(8): 26-29.
[13] YANG X M. Research progress in pharmacological activities of tetramethylpyrazine[J].Chin J Biochem Pharm (中国生化药物杂志), 2010,31(3):215-216.
[14] LEE L M, LIU C F, YANG P P. Effect of tetramethylpyrazine on lipid peroxidation in streptozotocin-induced diabetic mice[J]. Am J Chin Med, 2002, 30(4):601-608.
[15] YANG Q H, LIANG Y, XU Q, et al. Protective effect of tetramethylpyrazine isolated from Ligusticum chuanxiong on nephropathy in rats with streptozotocin-induced diabetes[J]. Phytomedicine, 2011, 18(13): 1148-1152.
[16] WANG X J,LIU C S, MING Y, et al.Effect of tetramethylpyrazine on activity of aldose reductase and on kidney cell apoptosis of diabetic nephropathy rat[J]. China J Tradit Chin Med Pharm (中华中医药杂志), 2009, 24(S1):60-61.
[17] MING Y,FENG L N,LIU H X, et al. Effect of tetramethylpyrazine and aminoguanidine on renal tissue nonenzymatic glycation and apoptosis in diabetic rats[J].Chin J Mod Drug Appl (中国现代药物应用),2010,4(15):144-145.
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脚注
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基金
广东省科技计划项目(2009B060700020)
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