肾乐和法安明防治大鼠肾小球硬化机制的探讨

作者	单位
王文新	WANG Wenxin, CHEN Xiangmei, YE Yizhou, et al. Nephrology Department, General Hospital of PLA, Beijing (100853
陈香美	WANG Wenxin, CHEN Xiangmei, YE Yizhou, et al. Nephrology Department, General Hospital of PLA, Beijing (100853
叶一舟	WANG Wenxin, CHEN Xiangmei, YE Yizhou, et al. Nephrology Department, General Hospital of PLA, Beijing (100853
师锁柱	WANG Wenxin, CHEN Xiangmei, YE Yizhou, et al. Nephrology Department, General Hospital of PLA, Beijing (100853

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中文摘要:

目的 :观察肾乐和法安明 (达肝素钠 )对 5/ 6肾切除大鼠残肾组织中Ⅳ型胶原和基质金属蛋白酶 9(matrixmetalloproteinase 9,MMP 9) /组织金属蛋白酶抑制物 1(tissueinhibitorsofmetalloproteinase 1,TIMP 1)基因表达的影响 ,旨在探讨两种药物对细胞外基质降解酶系MMP 9/TIMP 1的影响 ,从而进一步揭示其减轻肾小球硬化的机制。方法 :用 5/ 6肾切除的方法诱导大鼠局灶节段性肾小球硬化模型并给予肾乐 ( 4 g·kg- 1·d- 1)及法安明 ( 10 0 0IU·kg- 1·d- 1)治疗 2 0周 ,观察大鼠血压、蛋白尿、血肌酐、血脂和残余肾组织的病理改变程度 ,以及残肾组织Ⅳ型胶原、MMP 9的沉积和TIMP 1基因的表达。结果 :肾乐及法安明治疗能显著降低 5/ 6肾切除大鼠血压、蛋白尿、血肌酐、血脂和减轻肾组织的病理改变程度 ,并且显著减少残肾组织中Ⅳ型胶原、MMP 9的沉积以及下调Ⅳ型胶原、MMP 9/TIMP 1的基因表达 ;定量分析结果显示 ,与5/ 6Nx组比较 ,肾乐组和法安明组MMP 9的表达量分别下调了 30 0 %、2 8 5% ,TIMP 1的表达量分别下调了 59 3%、55 0 %。结论 :肾乐和法安明可能通过调节MMP 9/TIMP 1的基因表达 ,减轻肾小球重塑过程中细胞外基质的异常代谢和积聚 ,促进了细胞外基质的降解 ,这可能是肾乐和法安明防治肾小球硬

英文摘要:

To study the effects of Shenle and Fragmin on the degradation of extracellular matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinase-1 (TIMP-1) in the remnant kidneys of 5/6 nephrectomized rats treated with Shenle and Fragmin. Methods: The model of focal and segmental glomerulosclerosis was made by 5/6 nephrectomy in Wistar rats. After being treated with Shenle (4 g·kg -1 ·d -1 ) or Fragmin (1000IU·kg -1 ·d -1 ) for 20 weeks, the blood pressure, proteinuria, serum creatinine, lipids, renal pathological change of remnant kidney of the model animals were examined, and the mRNA expression of MMP-9, TIMP-1 and type Ⅳ collagen in the remnant kidney were also detected. Results: Shenle and Fragmin could significantly reduce the blood pressure, proteinuria, serum creatinine and lipids, alleviate the pathologic change of kidney tissue, decrease the type Ⅳ collagen, MMP-9 deposition. Shenle and Fragmin down-regulated the mRNA expression of MMP-9 by 30.0% and 28.5% and TIMP-1 expression by 59.3% and 55.0% in the remnant kidney of the 5/6 nephrectomized rats respectively. Conclusion: Shenle and Fragmin might ameliorate glomerulosclerosis through modulating MMP-9/TIMP-1 gene expression, alleviate the abnormal metabolism and accumulation, promote extracellular matrix degradation in glomeruli remodeling, it might be the important mechanism of Shenle and Fragmin in treating glomerulosclarosis.

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