雷公藤红素对狼疮鼠肾小球硬化的防治作用

目的　探讨雷公藤红素对狼疮性肾炎肾小球硬化的防治作用。方法　在不同发病时间、用不同剂量的雷公藤红素对BWF1小鼠进行连续 2 0周腹腔注射。运用考马斯亮蓝法检测 2 4h尿蛋白量 ;ELISA法检测血清抗dsDNA抗体水平 ;免疫组化法检测肾小球中纤维连接蛋白 (FN)、Ⅳ型胶原和基质金属蛋白酶 (MMP) 1、 2、 3与基质金属蛋白酶组织抑制剂 (TIMP) 1、 2的表达 ;逆转录 巢式PCR法检测小鼠肾组织中TGF β1的表达。结果　 (1)雷公藤红素能抑制小鼠蛋白尿产生 ,降低其血清抗dsDNA抗体水平 ,增加肾小球中MMP 1、 2而减少FN、Ⅳ型胶原和TIMP 1、 2与TGF β1的表达 ,改善小鼠组织学病变。 (2 )雷公藤红素于蛋白尿发生前较发生后使用疗效更为显著。 (3)于蛋白尿发生前使用雷公藤红素 3mg·kg-1·w-1和 6mg·kg-1·w-1的疗效差异无显著性。 (4)用药后各组间MMP 3的表达差异亦无显著性。结论　雷公藤红素对狼疮模型鼠的肾小球硬化具有明确保护作用 ;其降低肾脏FN、Ⅳ型胶原的沉积可能是通过增加肾组织局部MMP 1、 2而抑制TGF β1及TIMP 1、 2的表达而实现的。雷公藤红素对MMP 3的作用可能不及对MMP 1、 2的疗效明显。

The effect of tripterine in prevention of glomerulosclerosis in lupus nephritis mice

OBJECTIVE: To study the protective effects of Tripterine on experimental lupus nephritis glomerulosclerosis. METHODS: Different doses of Tripterine were injected peritoneally to BW F1 mice at different stages. 24-hour urine protein excretion, serum anti-dsDNA antibodies, renal pathology and RT-nested PCR were analyzed to study the preventive effects of Tripterine on LN glomerulosclerosis and its mechanisms. RESULTS: (1) Tripterine suppressed the development of proteinuria, decreased the level of serum anti-dsDNA antibodies, reduced the expressions of collagen type IV, fibronectin, TIMP-1, TIMP-2, TGF-beta(1) and improved the expressions of MMP-1, -2 in the murine kidney. (2) The use of Tripterine before occurrence of proteinuria had more obvious protective effects than its use after the occurrence of proteinuria. (3) No significant difference was found between the 3 mg/kg/week Tripterine-treated-group and the 6 mg/kg/week Tripterine-treated-group. (4) No obvious change was observed in the expression of MMP-3. CONCLUSIONS: Tripterine has a definite protective effect on glomerulosclerosis of the lupus murine model. The decrease of renal collagen type IV and fibronectin is probably due to its suppressive effect on the expressions of local TGF-beta(1) and TIMP-1, -2, and its improvement effect on the local expressions of MMP-1, -2. Tripterine may have no obvious influence on MMP-3 in this model.