雷公藤多苷对早期糖尿病肾病大鼠肾组织单核细胞趋化蛋白1及结缔组织生长因子表达的影响

Effects of triptergium glycosides on the expression of MCP-1 and CTGF in rats with early diabetic nephropathy

目的:观察不同剂量雷公藤多苷(TG)对早期糖尿病肾病(DN)大鼠肾组织单核细胞趋化蛋白1(MCP-1)及结缔组织生长因子(CTGF)表达的影响,探讨其保护肾脏的机制。方法:32只SD大鼠随机分正常对照(NC)组、糖尿病肾病(DN)组、小剂量TG干预(TG1)组及双倍剂量TG干预(TG2)组,8周后分别测定大鼠体重、血糖、血白蛋白(Alb)、尿素氮(BUN)、血清肌酐(SCr)及24h尿白蛋白定量(UTP);免疫组化法检测肾组织CTGF、MCP-1及单核巨噬细胞抗原(ED-1)表达,Western blotting及RT-PCR法分别检测CTGF、MCP-1蛋白及核酸表达。结果:与NC组相比,DN组大鼠血糖、Alb、BUN、SCr和UTP升高(P<0.05);与DN组相比,TG干预组Alb及UTP均明显好转(P<0.01),其中TG2组更明显;DN组肾组织ED-1阳性细胞数显著高于NC组(P<0.01),而TG1与TG2组较DN组明显减少(P<0.01),其中TG2组较明显。DN组肾组织CTGF、MCP-1蛋白及核酸表达显著增多(P<0.01),TG1及TG2组较DN组表达均明显减少,其中TG2组下降更明显。结论:MCP-1及CTGF可能参与DN发病及进展,TG可能通过下调其表达及减少巨噬细胞浸润起到肾脏保护作用,不同剂量TG对DN的干预效果不同,双倍剂量效果更显著。

Objective：To investigate the effect of different doses of Triptergium glycosides （TG） on the expression of monocyte chemoattractant protein-1 （MCP-1） and connective tissue growth factor （CTGF） in early diabetic nephropathy （DN） rats and to explore its mechanism of renal protection. Methodology ： Thirty two SD rats were randomly divided into normal control group （ NC, n = 8 ）, diabetic nephropathy group （ DN, n = 8 ）, DN treated with small dose of TG group （ TG1, n = 8） and double dose TG group （ TG2, n = 8 ）. After 8 weeks, the rat body weight, blood glucose （BG） , albumin （Alb） , BUN, SCr and 24 hours urinary total protein（UTP） were tested. The Expression of CTGF, MCP-1 and ED-1 was detected by immunohistochemistry. The gene and protein expression of CTGF and MCP-1 in renal tissue was detected by RT-PCR and western blotting. Results： Compared with NC group, the levels of BG, Alb, SCr, BUN and UTP were significantly increased in DN group （P〈0.01）. Compared with DN group, the levels of Alb and UTP were better significantly in TG group （P〈 0. 05） ,particularly in TG2 group. The number of ED-1 positive cells was increased significantly in DN group （ P〈0.01 ）, while which was inhibited by TG treatment （ in TG1 and TG2 group,P〈0.01 ） ,particularly in TG2 group. The expression of CTGF, MCP-1 and CTGF mRNA, MCP-1 mRNA was significantly increased （P〈0. 01 ） in DN group ,while which was also inhibited by TG treatment, particularly in TG2 group. Conclusion： MCP-1 and CTGF may be involved in the pathogenesis and progression of DN. TG can ameliorate the renal injury of diabetic rats by decreasing the MCP-1 and CTGF expression and reducing the activation of macrophages. The effects of different doses of TG on DN are different, double dose TG may be effective greater.