目的: 观察c-Jun氨基末端激酶(JNK)在慢性移植物抗宿主病(cGVHD)狼疮样小鼠肾组织中的表达情况,初步探讨其在狼疮肾炎肾脏纤维化中所起的作用。方法: 建立cGVHD狼疮样小鼠模型。将小鼠分为12周正常对照组、16周正常对照组、12周模型组及16周模型组4组,每组6只,于12周末处死12周正常对照组和12周模型组小鼠,16周末处死16周正常对照组和16周模型组小鼠,采用双缩脲比色法观察各组小鼠24 h尿蛋白排泄量,HE和Masson染色观察肾间质纤维化程度,免疫组织化学法定位检测JNK、p-JNK在肾组织的表达,RT-PCR法检测各组JNK mRNA表达及Western blotting技术半定量检测JNK、p-JNK蛋白表达水平。结果: 12周模型组小鼠24 h尿蛋白排泄量,JNK、p-JNK蛋白及mRNA的表达与正常对照组相比均明显增加(P <0.01),16周模型组更甚(P <0.01)。结论: JNK、p-JNK蛋白及mRNA表达在cGVHD狼疮样小鼠肾组织中明显上调,其可能在狼疮肾炎肾纤维化进程中起着重要作用。 |
Objective To explore the expression and significance of c-Jun N-terminal kinase (JNK)in renal tissue of murine with chronic graft-versus-host disease (cGVHD) lupus nephritis.Methods Mice models of cGVHD lupus nephritis were established according to relative literatures.Mice were randomly divided into four groups,control group of twelfth week (A,n=6),control group of sixteenth week (B,n=6), model group of twelfth week (C,n=6) and model group of sixteenth week (D,n=6).The mice of control group and model group of twelfth week were killed twelve weeks later and the mice of control group and model group of sixteenth week were killed sixteen weeks later respectively.Histological changes of kidney were observed by HE and Masson staining.The protein and mRNA expressions of JNK and p-JNK in renal tissue were detected by immunohistochemistry,Western blotting and RT-PCR respectively.Proteinuria was evaluated by biuret chromometry.Results Compared with the control groups,the urinary protein excretion,protein and mRNA expression of JNK and p-JNK were increased significantly in the model group of twelfth week respectively (P <0.01) and they were increased more significantly in the model group of sixteenth week (P <0.01).Conclusion The expression of JNK in renal tissue of murine with cGVHD is increased significantly,JNK maybe take an important part in the pathogenesis of murine lupus nephritis. |
[1] MA F Y,FLANC R S,TESCH G H,et al.A pathogenic role for c-Jun amino-terminal kinase signaling in renal fibrosis and tubular cell apoptosis[J].Journal of the American Society of Nephrology,2007,18 (2):472-484.
[2] 任文英,陈香美,邱全瑛,等.慢性移植物抗宿主病狼疮样肾炎小鼠模型的诱导[J].中国比较医学杂志,2004,14(4):215-222.
[3] YANG D D,KUAN C,WHITMARSH A J,et al.Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the JNK3 gene[J].Nature,1997,389(6653):865-870.
[4] KUMAGAE Y,ZHANG Y,KIM O J,et al.Human JNK expression and activation in the nervous system[J].Mol Brain Res,1999,67(1):10-17.
[5] OMORI S,HIDA M,ISHIKURA K,et al.Expression of mitogen-activated protein kinase family in rat renal development[J].Kidney Int,2000,58(1):27-37.
[6] 张梅,李晓玫.IgA肾病患者肾组织中丝裂素活化蛋白活化与肾小管上皮细胞转分化的关系[J].中华医学杂志,2004,84(11):898-903.
[7] SUGIURA T,IMAI E,MORIYAMA T,et al.Calcium channel blockers inhibit proliferation and matrix production in rat mesangials:possible mechanism of suppression of AP-1 and CREB activates[J].Nephron,2000,85(1):71-80.
[8] HOCEVAR B A,BROWN T L,HOWE P H,et al.TGFβ1 induces fibronectin synthesis though a c-Jun N-terminal kinase-dependent,Smad4-dependent parthway[J].EMBO J,1999,18(5):1345-1356.
[9] JIANG T,CHE Q,LIN Y F,et al.Aldose reductase regulates TGFβ1-indused production of fibronectin and type Ⅳ collagen in cultured rat mesangial cells[J].Nephrology,2006,11(2):105-112.
[10] BENNETT B L,SASAKI D T,MURRAY B W,et al.SP600125,an anthrapyrazolone inhibitor of Jun N-terminal kinase[J].Proc Natl Acad Sci USA,2001,98(24):13681-13686.
[11] 张爱华,黄松明,丁桂霞,等.c-Jun氨基末端激酶-激活蛋白-1信号通路调控血管紧张素诱导的单核细胞趋化蛋白1表达[J].中华病理学杂志,2004,33(6):550.
[12] EFERL R,WAGNER E F.AP-1:a double-edged sword intumorigenesis[J].Nat Rev Cancer,2003,3(11):859-868. |
