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目的以阳离子脂质体介导的转化生长因子-β1(TGF-β1)反义寡核苷酸(AODN)阻止TGF-β1的表达,观察其对大鼠使用环孢素A(CsA)后慢性肾毒性的防治作用。方法低盐饮食条件下,给SD雄性大鼠腹腔注射CsA 15 mg·kg-1·d-1,持续28 d;另两组在腹腔注射CsA的同时,于第15、20 d分别予以TGF-β1硫代磷酸AODN和阳离子脂质体包裹的TGF-β1硫代磷酸AODN尾静脉注射。检测各组血清肌酐的改变,组织形态学的变化;免疫组织化学法及聚合酶链式反应(RT- PCR)检测TGF-β1蛋白及其mRNA在组织的表达。结果成功地模拟了CsA对大鼠慢性肾毒性的病理改变。阳离子脂质体介导的TGF-β1硫代磷酸AODN可以显著抑制TGF-β1的表达,减轻CsA 所致慢性肾毒性的病理改变,并能改善肾功能。结论阳离子脂质体介导的TGF-β1硫代磷酸AODN通过抑制TGF-β1的表达,有效防治CsA对大鼠的慢性肾毒性。
Objective To investigate the effect of cationic liposome-mediated transforming growth factor-β1 (TGF-β1) antisense oligonucleotide (AODN) on the expression of TGF-β1 in rats. Nephrotoxicity prevention and treatment. Methods SD male rats were injected intraperitoneally with CsA 15 mg · kg-1 · d-1 for 28 days under low-salt diet. The other two groups were given CsA at the same time, β1 thiophosphate AODN and cationic liposome-encapsulated TGF-β1 phosphorothioate AODN tail vein injection. The changes of serum creatinine and histomorphology were detected in each group. The expression of TGF-β1 protein and its mRNA was detected by immunohistochemistry and polymerase chain reaction (RT-PCR). Results The pathological changes of chronic renal toxicity induced by CsA were successfully simulated. Cationic liposome-mediated TGF-β1 phosphorothioate AODN can significantly inhibit the expression of TGF-β1, reduce pathological changes of chronic nephrotoxicity induced by CsA, and improve renal function. Conclusion Cationic liposome-mediated TGF-β1 thiophosphoric acid AODN can effectively prevent chronic nephrotoxicity induced by CsA in rats by inhibiting the expression of TGF-β1.