多种免疫抑制剂对肾毒血清性肾炎大鼠肾组织中MMP-9的表达影响

目的探讨免疫抑制剂霉酚酸酯、来氟米特和他克莫司对肾毒血清性肾炎大鼠肾组织中基质金属蛋白酶-9表达的影响。方法制备肾毒血清性肾炎大鼠模型,并随机分为病理对照组、霉酚酸酯治疗组、来氟米特治疗组和他克莫司治疗组,每组各10只。各治疗组均给予相应药物灌胃给药每天1次,2周后观察血清总蛋白(Tp)、白蛋白(Alb)、血肌酐(Scr)和尿素氮(BUN)水平。应用免疫组织化学观察肾组织中基质金属蛋白酶-9的表达。结果基质金属蛋白酶-9在病理对照组肾小球和肾小管中的表达均较正常对照组增高(P<0.01);与病理对照组比较,霉酚酸酯、来氟米特和他克莫司治疗后可使其表达减少(P<0.01),且来氟米特治疗组较其它两用药组下降明显(P<0.05)。各治疗组与病理对照组比较Tp、Alb增加(P<0.01),Scr、BUN降低(P<0.01)。结论霉酚酸酯、来氟米特和他克莫司治疗均能减少肾毒血清性肾炎大鼠肾组织中基质金属蛋白酶-9的表达,改善肾功能,其中来氟米特效果最理想。

The effect of newer immunosuppressive on the expression of MMP-9 in nephrotoxic nephritis in rats

Objective To investigate the effects of immunosuppressive agents such as Mycohonolate mofetil (MMF),Leflunomide (LEF) and tarcrolimus (FK506) therapy on the expression of MMP-9 in rats with Nephrotoxic Nephritis. Methods Nephrotoxic Nephritis was induced in the other 40 rats and these rats were randomly divided into four groups: nephritis group, MMF therapy group,LEF therapy group and FK506 therapy group. Each of the therapy groups was given intragastric administration once every day. After 2 weeks, serum Total Protein (Tp), Albumin (Alb), Blood Urea Nitrogen (BUN) and Serum creatine (Scr) of every rat were determined. Immunohistochemistry was used to evaluate the change and expression of MMP-9 in the tissues of kidney. Results The expression of MMP-9 in glumeruli and renal tubles in the nephritis group was much higher than that in nomal group (P<0.01), The expression in therapy groups was much lower than that in nephritis group(P<0.01),and in LEF therapy group it was much lower than other groups(P<0.05). The thrapy groups had much higher Tp and Alb level and much lower BUN and Scr level than the nephritis group(P<0.01).Conclusion MMF, LEF, and FK506 reduces the expression of MMP-9 in the tissues of kidney, with preservation of renal function in experimental crescentic glomerulonephritis, meanwhile LEF has the best effect in three therapy groups.