青蒿琥酯对糖尿病肾病大鼠肾功能和单核细胞趋化蛋白-1及肿瘤坏死因子-α的影响  

Influences of Artesunate on Renal Function and MCP-1,TNF-α of Diabetic Nephropathy Rats

作　　者：聂寒 苏珂[1] 龙艳[1] 蒋姗姗[1] 

机构地区：[1]桂林医学院附属医院内分泌科,桂林541000

出　　处：《医药导报》2015年第5期593-597,共5页Herald of Medicine

基　　金：广西医疗卫生适宜技术研究与开发项目(S201316-07);广西自然科学基金项目(2012GXNSFAA053085)

摘　　要：目的观察青蒿琥酯对糖尿病肾病大鼠肾功能及单核细胞趋化蛋白-1(MCP-1)、肿瘤坏死因子-α(TNF-α)表达的影响。方法雄性斯泼累格·多雷(SD)大鼠36只,随机分为6组,每组6只:正常对照组,模型对照组,青蒿琥酯小剂量组(10 mg·kg-1·d-1)、中剂量组(20 mg·kg-1·d-1)、大剂量组(30 mg·kg-1·d-1),依那普利组(10 mg·kg-1·d-1)。采用高糖高脂饮食联合一次性腹腔注射小剂量链脲佐菌素法建立2型糖尿病肾病模型。分别干预8周后,检测各组大鼠血糖、24 h尿蛋白定量、血肌酐、尿素氮等评估肾功能情况;光镜下观察肾组织病理形态学变化;检测大鼠血清MCP-1、TNF-α水平。结果与模型对照组比较,各治疗组24 h尿蛋白、血肌酐、血尿素氮、血糖均一定程度下降(均P<0.01),尤以青蒿琥酯中、大剂量组下降更显著(均P<0.01)。模型对照组MCP-1及TNF-α的含量分别为(181.71±23.06),(3.98±0.24)pg·m L-1;青蒿琥酯小剂量组分别为(157.47±38.53),(3.14±0.38)pg·m L-1,中剂量组分别为(138.65±18.03),(2.58±0.11)pg·m L-1,大剂量组分别为(105.09±12.64),(2.25±0.16)pg·m L-1,均显著降低(均P<0.05)。结论青蒿琥酯对2型糖尿病肾病具有一定的治疗作用,其机制可能部分是通过减少炎性因子MCP-1、TNF-α的分泌,抑制肾脏炎性反应,调节肾功能,缓解肾脏的病理损伤,从而延缓肾脏病变的发展。Objective To investigate the effects of artesunate（ Art） on renal function and the expression of monocyte chemotactic protein-1（MCP-1）and tumor necrosis factor-α（TNF-α）in rats with type 2 diabetic nephropathy（DN）. Methods Thirty six male SD rats were randomly divided into six groups, six rats in each, as the normal control, model control, low-dose Art, middle-dose Art, high-dose Art groups which were intragastrically administrated with Art at the dose of 10, 20 and 30 mg·kg^-1 ·d^-1 for consecutive 8 weeks, enalapril group, which were intragastrically administrated with enalapril 10 mg·kg^-1 ·d^-1 for consecutive 8 weeks. Rats were injected with low dosage streptozotocin and fed with high fat and high＆amp;nbsp;sugar diets to establish type 2 diabetic nephropathy rat model. After 8 weeks’ treatment, the plasma glucose, 24-hour urine protein, serum creatinine and blood urea nitrogen were measured to evaluate renal function. The pathological morphology of rats was performed. Immunohistochemistry and enzyme linked immunosorbent assay （ ELISA ） were performed to examine the expression levels of MCP-1 and TNF-α,respectively. Results Compared with the model control group, 24-hour urine protein, serum creatinine, blood urea nitrogen and blood glucose were significantly decreased in the treatment groups （P〈0. 01）. Art significantly decreased the serum expressions of MCP-1 and TNF-α in low-, middle-, high-dose Art group （ 157. 47 ± 38. 53, 138.65±18.03,105.09±12. 64 and 3. 14±0. 38,2. 58±0. 11,2. 25±0. 16） pg·mL^-1, compared with model control group （181.71±23.06 and 3. 98±0. 24） pg·mL^-1（P〈0. 05）. Conclusion Art has beneficial effects on type 2 diabetic nephropathy. The mechanism of which may be related to the inhibition of inflammatory factor MCP-1 and TNF-α,further relive the pathological injury of kidney and delay the progress of diabetic nephropathy to some extent.

关 键 词：青蒿琥酯 肾病 糖尿病 肿瘤坏死因子 单核细胞趋化蛋白 

分 类 号：R282.71[医药卫生—中药学] R285.5[医药卫生—中医学]