fk506治疗大鼠早期膜性肾病的实验研究

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1、FK506治疗大鼠早期膜性肾病的实验研究作者：贾冶王晶顾华吴曼郭桥艳徐锋刘庆鑫许钟镐苗里宁【摘要】目的观察FK506治疗大鼠膜性肾病的疗效。方法复制Wistar大鼠膜性肾病模型。实验分为3组：正常组(N组)，模型组(M组)，FK506治疗组(FK506组)，每组12只。用阳离子化牛血清白蛋白制作大鼠膜性肾病模型,于正式免疫开始后2、4、6、8w检测大鼠24h尿蛋白定量;最后心脏取血，测定血清肌酐、尿素氮、白蛋白水平。处死大鼠后取肾观察肾组织病理改变;应用免疫组织化学方法检测肾组织中TGFβ1与NFκB的表达，应用Western印迹法

2、测定大鼠肾组织中TGFβ1蛋白表达的变化。结果M组与N组相比出现大量蛋白尿，血清白蛋白水平降低。免疫组化检测结果示M组TGFβ1和NFκB的表达均高于N组，而FK506组的水平低于M组。Western印迹法显示M组及FK506组TGFβ1高于N组，FK506组的水平低于M组。结论FK506能降低膜性肾病大鼠尿蛋白，提高血清白蛋白，可抑制肾组织TGFβ1与NFκB的表达，用其防治大鼠早期膜性肾病有较好的疗效。【关键词】FK506;TGFβ1;膜性肾病11　　【Abstract】ObjectiveToinvestigateth

3、eeffectofFK506onthemembranousnephropathyinrat.MethodsMembranousnephropathyratswereinducedbyCBSA.Wistarratsweredividedintonormalcontrol(N),membranousnephropathy(M),andFK506treatment(FK506)groups.Urinaryproteinexcretionwasmeasuredat2,4,6,8wfromthebeginningofimmunization.T

4、heratbloodwasobtainedviacardiacpuncture,andthekidneyswereremoved.ThebloodsamplesweresavedformeasuringthelevelsofserumBUN,ScrandALB.Kidneyspecimenswereroutinelyprocessedforlightmicroscopy.ImmunohistochemistrymethodwasperformedtoobservetheexpressionsofTGFβ1andNFκB.TGFβp

5、roteinexpressionwasmeasuredbyWesternblot.ResultsUrinaryproteinexcretioningroupMwassignificantlyhigherthanthatingroupN.ThelevelofserumALBingroupMwaslowerthanthatingroupN.UpregulationofTGFβ1andNFκBexpressionwereobservedinimmunohistochemicalfindings.Conclusionswiththatin

6、Mgroup,urinaryproteinexcretionwassignificantlydecreasedandthelevelofserumALBwassignificantlyincreasedinFK506group.ImmunohistochemistryshowedthattheexpressionsofTGFβ1andNFκBweresignificantlylowerinFK506groupthanthoseingroupM.TheTGFβ1proteinexpressionwassignificantlylow

7、erinFK50611groupthanthatinMgroupbyWesternblot.ConclusionsFK506canreduceurinaryproteinexcretion,increasethelevelofALB,improvekidneypathologicalchanges,inhibitTGFβ1overexpressionandNFκBactivationinrenaltissueofmembranousnephropathyrats,andcanbeusedfortreatmentofearlymemb

8、ranousnephropathy.　　【Keywords】FK506;TGFβ1;Membranousnephropathy　膜性肾病(membranousnephropathy，MN)是中老年人常见的