α－促黑素对大鼠肾肺缺血／再灌注损伤的保护作用和机制研究

The protective effect of alpha-melanocyte stimulating hormone against kidney and lung ischemia reperfusion injury in rats and its potential mechanisms

目的：探讨大鼠肾缺血／再灌注（I／R）损伤中趋化因子2（CXCL2）、转化生长因子－α（ TGF－α）的表达及α－促黑素（α－MSH）的治疗作用。方法将30只健康雄性SD大鼠随机分为假手术组、I／R组和α－MSH治疗组，每组各10只大鼠。通过阻断双侧肾动脉建立大鼠肾I／R模型，并在α－MSH干预后24 h处死各组大鼠，留取血液及肾、肺组织。经HE染色后在光镜下观察肾、肺组织病理变化，采用RT－PCR和ELISA方法检测大鼠肾、肺组织中CXCL2、TGF－αmRNA和蛋白表达水平。结果①I／R组血清BUN和Cr水平均高于假手术组和α－MSH治疗组（ P＜0．05），假手术组和α－MSH治疗组血清BUN和Cr水平比较差异均无统计学意义（ P＞0.05）。②肾、肺组织中α－MSH治疗组CXCL2 mRNA低于I／R组（P＜0．05），而TGF－αmRNA高于I／R组（P＜0．05）。③I／R组和α－MSH治疗组CXCL2、TGF－α蛋白表达值均高于假手术组（P＜0．05）；α－MSH治疗组CXCL2蛋白表达值低于I／R组（P＜0．05），而α－MSH治疗组TGF－α蛋白表达值高于I／R组（ P＜0．05）。结论α－MSH可能通过增加TGF－α表达水平和减少CXCL2表达水平，减轻肾I／R所导致的肾、肺组织的损伤。

Objective To explore the protective effect of alpha -melanocyte stimulating hormone （α-MSH） and the mRNA and protein expression of chemokine （ C-X-C motif） ligand 2 （ CXCL2） and transforming growth factor -α（ TGF -α） in rats with kidney and lung ischemia reperfusion injury.Methods A total of 30 healthy male S-D rats were randomly divided into three groups：control group, renal ischemia -reperfusion （ I/R） andα-MSH group.The model of acute ischemic kidney injury in rats was made by blocking bilateral renal artery with clamps.All rats were sacrificed after 24 h of modeling, kidney and lung tissue of rats was sampled and stained with hematoxylin-eosin （ HE ） staining method, and the pathological changes of kidney and lung were observed under microscope.Blood samples were collected to detect the serum blood urea nitrogen （ BUN） and creatinine （ Cr） , the mRNA and protein expression of CXCL2 and TGF-αwas respectively detected by RT-PCR and ELISA.Results ①The value of BUN and Cr in I/R group was higher than those in control and α-MSH group （P〈0.05）, and no significant difference was detected between control andα-MSH group （P＆gt;0.05）.②The levels of mRNA expression of CXCL2 inα-MSH group were lower than those in I/R group （ P〈0.05） , while the levels of mRNA expression of TGF-αinα-MSH group were higher than those in I/R group （ P〈0.05）.③The levels of protein expression of ＆CXCL2 and TGF-αin α-MSH and I/R group were higher than those in control group （P〈0.05）;the levels of protein expression of CXCL2 in α-MSH group is lower than those in I/R group （ P〈0.05）, while the levels of protein expression of TGF-αin α-MSH group is higher than those in I/R group （P〈0.05）.Conclusion α-MSH may increase the protein and mRNA expression of TGF-αand decrease the protein and mRNA expression of CXCL2, which probably is one of the mechanisms that reduce the kidney and lung injury among rats with I/R.