Wan Yi-gang, Sun Wei, Shmizu Fujio, Gu Liu-bao, Suziki Koichi, Karasawa Tamaki, Kawachi Hiroshi
The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu, China.
Zhongguo Zhong Yao Za Zhi. 2005 Mar;30(5):361-5.
To examine suppressive effects of multi-glycoside of Tripterygium wilfordii Hook. f. (GTW)on mesangial injury induced by two-injecti on of anti-Thy1. 1 monoclonal antibody(mAb) 1-22-3 in vitro.
We established the irreversible model of glomerulosclerosis with anti-Thy1. 1 mAb 1-22-3. After 42 days of oral treatment with GTW (50 mg x kg(-1) BW)and vehicle (distilled water), to observe effects of GTW on proteinuria, renal function, mesangial morphological change, and mRNA expressions of collagen type I and TGF-beta by light microscope (LM), immunofluorescence (IF), and Reverse Transcription Polymerase Chain Reaction (RT-PCR).
GTW ameliorated proteinuria (from day24 to day 42) and mesangial proliferation [total cell number, GTW group 65.67+/-3.43 vs. control group 87.02+/-2.41, P < 0.05; matrix expansion, GTW group 1.20+/-0.06 vs. control group 2.77+/-0.23, P < 0.05; alpha-smooth muscle actin(alpha-SMA) expression, GTW group 1.75+/-0.33 vs. control group 2.62+/-0.15, P < 0.05; collagen type I expression, GTW group 1.68+/-0.31 vs. control group 2.06+/-0.24, P < 0.05], moreover, significantly reduced the glomerular expression of mRNA for collagen type 1(53.5% to the control group, P < 0.05)and TGF-beta(14.7% to the control group, P < 0.05)on day 42day.
GTW can not only decrease proteinuria, but also ameliorate mesangial alterations probably by the reduction of cytokines. GTW may be a promising agent for the prevention of progressive and irreversible glomerulosclerosis.
研究雷公藤多苷(GTW)对体外两次注射抗Thy1.1单克隆抗体(mAb)1-22-3诱导的系膜损伤的抑制作用。
我们用抗Thy1.1 mAb 1-22-3建立了肾小球硬化的不可逆模型。用GTW(50 mg·kg⁻¹体重)和赋形剂(蒸馏水)口服治疗42天后,通过光学显微镜(LM)、免疫荧光(IF)和逆转录聚合酶链反应(RT-PCR)观察GTW对蛋白尿、肾功能、系膜形态变化以及Ⅰ型胶原和转化生长因子-β(TGF-β)mRNA表达的影响。
GTW改善了蛋白尿(从第24天到第42天)和系膜增生[总细胞数,GTW组65.67±3.43对对照组87.02±2.41,P<0.05;基质扩张,GTW组1.20±0.06对对照组2.77±0.23,P<0.05;α-平滑肌肌动蛋白(α-SMA)表达,GTW组1.75±0.33对对照组2.62±0.15,P<0.05;Ⅰ型胶原表达,GTW组1.68±0.31对对照组2.06±用0.24,P<0.05],此外,在第42天显著降低了肾小球Ⅰ型胶原mRNA表达(为对照组的53.5%,P<0.05)和TGF-β mRNA表达(为对照组的14.7%,P<0.05)。
GTW不仅可以降低蛋白尿,还可能通过减少细胞因子来改善系膜改变。GTW可能是预防进行性和不可逆性肾小球硬化的一种有前景的药物。