臭氧氧化后处理对肾脏缺血再灌注损伤的作用

摘要：目的  研究臭氧O3氧化后处理对大鼠肾脏缺血再灌注所致肾脏慢性纤维化的作用及相关机制。方法  将72例SD大鼠随机分为4组：假手术组（S组）、单纯缺血再灌注组（I/R组）、O3氧化后处理组（I/R+O3组）、氧气O2后处理组（I/R+O2组），每组4只。每组在模型复制成功后2周检测血清肌酐（Scr）和血浆尿素氮（BUN），2和10周取肾脏标本，进行苏木精-伊红染色法染色、Masson染色，以及免疫组织化学法检测转化生长因子β1（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）的表达。结果  术后2周各组的血清Scr、血浆BUN基本恢复到正常范围，两组比较，差异无统计学意义（P >0.05）。术后10周Masson染色显示，肾纤维化程度，其他3组较S组重（P <0.05），I/R+O3组较I/R组、I/R+O2组轻（P <0.05），而I/R组与I/R+O2组比较，差异无统计学意义（P >0.05）。与S组比较，其他3组TGF-β1、α-SMA的表达增强（P <0.05）；与I/R组比较，I/R+O3组的表达减弱（P <0.05）；I/R组与I/R+O2组比较，差异无统计学意义（P >0.05）。结论  O3后处理可以减轻缺血再灌注损伤肾脏的慢性纤维化，其机制可能与O3后处理抑制转化生长因子-β1/Smad信号通路激活有关。

Ozone oxidative post-conditioning protects rat kidney from ischemia reperfusion injury

Abstract: Objective To explore the effect of ozone oxidative post-conditioning on chronic renal fibrosis induced by ischemia reperfusion injury in rats and the mechanism. Methods Totally 72 adult male SD rats were randomly divided into four groups (18 in each): sham-operation control group (S group), ischemia reperfusion group (I/R group), ozone oxidative post-conditioning group (I/R+O3 group) and oxygen post-conditioning group (I/R+O2 group). Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were evaluated 2 w after successful modeling. Renal specimens were obtained in the 2th and 10th week respectively, and the renal tissues were stained by HE and Masson staining. The protein expressions of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) were determined by immunohistochemistry analysis. Results After two weeks of treatment, Scr and BUN of each group basically returned to normal levels, and there were no significant differences among the four groups (P > 0.05). Ten weeks after operation, Masson staining revealed renal fibrosis of the I/R, I/R+O2 and I/R+O3 groups was more serious than that of the S group (P < 0.05), renal fibrosis of the I/R+O3 group was milder than taht of the I/R and I/R+O2 groups (P <0.05), while there was no difference between the I/R group and the I/R+O2 group (P > 0.05). The protein expressions of TGF-β1 and α-SMA of the I/R, I/R+O2 and I/R+O3 groups were higher than those of the S group (P < 0.05); and compared with the I/R group, the expressions of TGF-β1 and α-SMA were lower in the I/R+O3 group (P < 0.05). There was no difference in the expression of TGF-β1 or α-SMA between the I/R+O2 group and the I/R group (P > 0.05). Conclusions Ozone oxidative post-conditioning can relieve chronic renal fibrosis caused by ischemic reperfusion injury, and inhibition of activation of TGF-β1/Smad signaling pathway may be one of the mechanisms.