机构地区:[1]上海交通大学儿童医院新生儿科,上海200040 [2]上海交通大学儿童医院重症监护病房,上海200040
出 处:《上海交通大学学报(医学版)》2009年第10期1169-1173,共5页Journal of Shanghai Jiao tong University:Medical Science
基 金:上海市卫生局基金(05041)~~
摘 要:目的探讨内毒素休克大鼠肾组织Toll样受体2(TLR2)mRNA和TLR4 mRNA的表达变化,以及血管活性肠肽(VIP)和甲基泼尼松龙(MP)的作用及可能机制。方法采用大肠杆菌脂多糖(LPS)(E coliO55:B5)10 mg/kg静脉注射,建立大鼠内毒素休克模型(LPS组,n=16);LPS+VIP组(n=16)建模后注射VIP(5 nmol/kg),LPS+VIP+MP组(n=16)注射VIP(5 nmol/kg)和MP(3 mg/kg);另设生理盐水对照组(n=8)。透射电子显微镜观察LPS注射6 h和24 h大鼠肾组织病理学变化;RT-PCR测定肾组织TLR2 mRNA和TLR4 mRNA的表达。结果建模后6 h,电子显微镜下见LPS组肾小球毛细血管内皮细胞肿胀,线粒体空泡变性;建模后24 h,可见LPS组肾小管细胞线粒体肿胀、空泡变性,细胞核轻度固缩;LPS+VIP组及LPS+VIP+MP组肾组织病变轻于同期LPS组。LPS注射6 h,LPS组、LPS+VIP组及LPS+VIP+MP组肾组织TLR2 mRNA和TLR4 mRNA表达均高于对照组(P<0.01);LPS注射24 h,LPS组TLR2 mRNA和TLR4 mRNA表达高于其他组(P<0.01)。结论内毒素休克大鼠肾组织TLR2 mRNA和TLR4 mRNA表达增强;VIP和MP干预可减轻肾脏损伤,可能与其下调TLR2 mRNA和TLR4 mRNA的表达有关。Objective To investigate the expression of Toll like receptor 2(TLR2) mRNA and TLR4 mRNA in renal tissues of rats with endotoxin-induced shock,and explore the possible effects and mechanism of vasoactive intestinal peptide(VIP) and methylprednisolone(MP) on renal injury. Methods Endotoxin(E coli O55:B5 LPS,10 mg/kg) was injected intravenously to the rats to establish the endotoxin-induced shock models(LPS group,n=16).The rats in LPS+VIP group(n=16) was injected with VIP(5 nmol/kg) after model establishment,and those in LPS+VIP+MP group(n=16) was injected with VIP(5 nmol/kg) and MP(3 mg/kg) after model establishment.Besides,normal saline control group(control group) was established(n=8).Electron microscope was used to observe the histopathological changes in renal tissues 6 h and 24 h after model establishment,and RT-PCR was performed to evaluate the expression of TLR2 mRNA and TLR4 mRNA in renal tissues. Results Six h after model establishment,glomerular endothelial cell swelling and vacuolar degeneration of mitochondria were observed in LPS group under electronic microscope.Twenty-four h after model establishment,mitochondrial swelling,vacuolar degeneration and slight nucleus pyknosis of renal tubular cells were observed in LPS group.The renal pathological changes in LPS+VIP group and LPS+VIP+MP group were much less severe than those in LPS group at the same time.The expression of TLR2 mRNA and TLR4 mRNA in LPS,LPS+VIP and LPS+VIP+MP groups was significantly higher than that in control group 6 h after LPS injection(P〈0.01),while the expression of TLR2 mRNA and TLR4 mRNA in LPS group was higher than that in the other groups 24 h after LPS injection(P〈0.01). ConclusionThe expression of TLR2 mRNA and TLR4 mRNA in renal tissues of rats with endotoxin-induced shock is markedly up-regulated.VIP and MP can obviously alleviate renal pathological changes,and the mechanism may contribute to impacting on the expression of TLR2 mRNA and TLR4 mRN
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