摘要
目的 探讨TGF β1在CsA慢性肾毒性中的作用。方法 低盐饮食的条件下 ,给SD雄性大鼠腹腔注射CsA ( 15mg·kg-1·d-1) ,持续 2 8d ;另外两组在腹腔注射CsA的同时 ,于第 15、2 0天分别予以TGF β1硫代AODN、阳离子脂质体包裹的TGF β1硫代AODN尾静脉注射 ,免疫组化法及逆转录聚合酶链式反应 (RT PCR)检测TGF β1蛋白及其mRNA在组织的表达 ,检测各组组织形态学的变化。结果 建立大鼠CsA慢性肾毒性模型 ,显示了CsA慢性毒性的病理改变 ;在CsA慢性肾毒性组织中 ,TGF β1的mRNA及蛋白表达显著增加 ;阳离子脂质体介导的TGF β1硫代AODN可以显著抑制TGF β1的表达 (P <0 .0 1) ,减轻CsA慢性肾毒性的病理改变。结论 ①阳离子脂质体介导的TGF β1硫代AODN可以显著抑制TGF β1的表达 ,减轻CsA慢性肾毒性病理改变 ,改善肾功能 ;②CsA慢性肾毒性与TGF β1的表达显著增加有关。
Objective To study the roles of transforming growth factor-β1 (TGF-β1) in cyclosporin A (CsA)-induced nephrotoxicity and the inhibitory effect of cationic liposome-mediated antisense oligonucleotides (AODN) on TGF-β1. Methods CsA (15 mg·kg -1 ·d -1 ) was intraperitoneally injected into SD male rats on low salt diet consecutively for 4 weeks. Rats in the other two groups were injected in the caudal veins with additional TGF-β1 AODN and cationic liposome-encapsulated TGF-β1 AODN at 15 and 20 d, respectively. TGF-β1 protein expression and TGF-β1 mRNA expression in tissues were detected by immunohistochemistry and RT-PCR. The morphological changes of tissues in each group were also observed. Results Under the condition of low salt diet, a rat model of CsA-induced nephrotoxicity was established. The expressions of TGF-β1 mRNA and protein increased significantly in CsA-treated rats. RT-PCR confirmed that the expression of TGF-β1 mRNA decreased significantly in cationic liposome-mediated AODN rats (P<0.01). Immunohistochemistry revealed that the expression of TGF-β1 protein was inhibited significantly (P<0.01) in the liposome-mediated AODN rats with a comparable effect on the prevention of CsA-induced chronic nephrotoxicity. Conclusion CsA-induced chronic nephrotoxicity is related to the expression of TGF-β1. After inhibition of the expression of TGF-β1, liposome-mediated antisense oligonucleotide can attenuate the structural changes of kidney in CsA-induced chronic nephrotoxicity.
出处
《局解手术学杂志》
2004年第2期78-80,共3页
Journal of Regional Anatomy and Operative Surgery
