不同浓度七氟烷后处理对大鼠肾脏缺血／再灌注损伤的影响

Effects of sevoflurane postconditioning on renal ischemia-reperfusion injury ：experiment with rats

目的探讨不同浓度七氟烷后处理对大鼠肾脏缺血／再灌注损伤的影响，评价七氟烷后处理对大鼠肾脏缺血／再灌注损伤后。肾内皮型一氧化氮合成酶（eNOS）、诱导型一氧化氮合成酶（iNOS）的影响。方法SD雄性大鼠60只，随机分为5组（每组12例）：假手术组、缺血／再灌注组[建立肾脏缺血／再灌注（I／R）模型]、不同浓度七氟烷后处理组[（1．2％七氟烷为S1,2组，1．8％七氟烷为S1.8组和2．2％七氟烷为S2.2组）：先建立I／R模型，在缺血后再灌注的同时用不同浓度的七氟烷处理2h，测定再灌注24h时血清肌酐（Cr）、尿素氮（BUN）浓度；大体标本观察再灌注肾横切面坏死情况；光镜下观察肾皮质肾小管坏死百分率]。为探讨七氟烷后处理作用机制，采用免疫组化法测假手术组，缺血／再灌注组，S1.8组肾组织eNOS、iNOS的表达。结果再灌注24h时，与假手术组相比，其余4组血清Cr、BUN、肾小管坏死率明显升高（P〈0．05）；与缺血／再灌注组相比，S1.2组、S1.8组、S2.2组血清Cr、BUN、肾小管坏死率明显下降（P〈0．05）；S1.2组、S1.8组、S2．2组之间上述各指标差异无统计学意义（P〉0．05）。与假手术组相比，缺血／再灌注组肾eNOS、iNOS的表达明显增强（P〈0．05）；与缺血／再灌注组相比，S1.8组肾eNOS、iNOS的表达明显下降（P〈0．05）。结论七氟烷后处理可以减轻大鼠。肾缺血／再灌注损伤；七氟烷3种不同浓度（1．2％，1．8％，2．2％）后处理对减轻大鼠缺血／再灌注损伤无明显差别；七氟烷后处理可抑制肾eNOS、iNOS的表达。

Objective To investigate the protective effects of postconditioning with different concentrations of sevoflurane on renal ischemia-reperfusion （I/R） injury. Methods The following procedures were performed on 48 male SD rats to establish I/R models： the right kidney and ureter were resected, and the left renal arteries and veins were occluded by atraumatic clamps for 45 rain and then the clamps were removed to provide reperfusion for 24 h. And the rats were randomly divided into 4 equal groups; I/R Group, S1.2 Group inbreathing 1.2% sevoflurane simultaneously since the beginning of reperfusion for 2 h, S1.8 Group inbreathing 1.8% sevoflurane simultaneously since the beginning of reperfusion for 2 h, and S2.2 Group inbreathing 2. 2% sevoflurane simultaneously since the beginning of reperfusion for 2 h. Another 12 rats underwent resection of the right kidney and ureter and exposure of the left renal arteries and veins only for 45 min. The rates were killed at the end of 24h reperfusion. Blood samples were taken for determination of serum creatinine （Cr） and blood urea nitrogen （BUN）. The left kidneys were harvested to undergo microscopy to observe the percentage of pyknotic nuclei in cortical tubular cells. Immunohistochemistry was used to detect the expression of endothelial nitric oxide synthase （eNOS） and inducible nitric oxide synthase （iNOS） in the kidney. Results The necrotic rate of renal tubule of the Sham Group was significantly lower than those of the other 4 groups （ all P 〈 0. 01 ）, and the necrotic rates of renal tubule of the S1.2, S1.8 , and S2.2 Groups were all significantly lower than that of I/R Group （ all P 〈 0. 05）. The levels of blood Cr and BUN, and the percentage of pyknotic nuclei in cortical tuber cells of I/ R, S1.2, S1.8, and S2.2 Groups were all significantly higher than those of Sham Group（all P 〈 0. 05）and these indexes listed above of S1.2 , S1.8, and S2.2 Groups were all significantly lower than those of I/R Group （all P 〈0. 05）. However, there were not significant differences in these indexes among S1.2 ,S1.8 , and S2.2 Groups （ all P 〉 0. 05 ）. The kidney eNOS and iNOS expression levels of I/R Group were both significantly higher than those of Sham Group （both P 〈0. 05）, and the kidney eNOS and iNOS expression levels of S,s Group were both significantly lower than those of I/R Group （ both P 〈 0. 05 ）. Conclusion Sevoflurane postconditioning attenuates the renal damage induced by I/R and down-regulates the eNOS and iNOS expression in kidney. Different concentrations do not show different effects.