下调PAR-1对脑出血模型大鼠的干预效果及作用机制

The intervention effect and mechanism of down regulating PAR-1 on cerebral hemorrhage model rats

目的探讨下调蛋白酶激活受体-1(Proteinase activated receptor-1,PAR-1)对脑出血模型大鼠的干预效果及相关作用机制。方法选取40只健康清洁级雄性大鼠,建立脑出血模型,分为假手术组10只,模型组、对照(pcDNA3-PARls)组、下调PAR-1(PcDNA3-PARlas)组各9只,表达载体构建,评估神经功能评分,检测脑水肿体积、脑组织含水量,脑组织HE染色,检测丙二醛(Malondialdehyde,MDA)水平、超氧化物歧化酶(Superoxide dismutase,SOD)活性、炎症因子及PAR-1相对表达水平。结果模型组、对照组、下调PAR-1组神经功能评分、脑组织含水量、MDA水平,MMP-9,TNF-α,IL-1β,PAR-1相对表达水平高于假手术组,SOD活性低于假手术组(P<0.05);对照组神经功能评分、脑水肿体积、脑组织含水量、MDA水平,MMP-9,TNF-α,IL-1β,PAR-1相对表达水平高于模型组,SOD活性低于模型组(P<0.05);下调PAR-1组神经功能评分、脑水肿体积、脑组织含水量、MDA水平,MMP-9,TNF-α,IL-1β,PAR-1相对表达水平低于模型组和对照组,SOD活性高于模型组和对照组(P<0.05)。结论下调PAR-1对脑出血模型大鼠干预效果显著,能减轻大鼠脑水肿,可能通过下调PAR-1表达来降低MMP-9,TNF-α,IL-1β水平和调控氧自由基代谢,从而对脑出血后的脑组织起到一定的保护作用。

Objective To study the effect of down-regulation of protease activated receptor-1(PAR-1) on rats with cerebral hemorrhage and its mechanism.Methods 40 healthy and clean male rats were selected to establish the model of cerebral hemorrhage, which was divided into sham operation group(10 rats), model group(9 rats), control(pcDNA3-PARls) group(9 rats), down regulated PAR-1(pcDNA3-PARlas) group(9 rats). Expression vector was constructed, neurological function score was evaluated, brain edema volume and brain water content were detected, pathological tissue was stained by HE, malondialdehyde(MDA), superoxide dismutase(SOD), inflammatory factor and PAR-1 expression levels were detected.Results The neurological function score, brain water content, MDA, MMP-9, TNF-α, IL-1β, PAR-1 relative expression levels of model group, control group, down regulated PAR-1 group were higher than those of sham operation group, and the activity of SOD was lower than that of sham operation group(P<0.05). The neurological function score, brain edema volume, brain water content, MDA, MMP-9, TNF-α, IL-1β, PAR-1 relative expression levels of control group were higher than those of model group, and the activity of SOD was lower than that of model group(P<0.05). The neurological function score, brain edema volume, brain water content, MDA, MMP-9, TNF-α, IL-1β, PAR-1 relative expression levels of down regulated PAR-1 group were lower than those of model group and contral group, and the activity of SOD was higher than that of model group and contral group(P<0.05).Conclusion Down regulation of PAR-1 had the significant effect on the intervention of cerebral hemorrhage model rats, which could reduce brain edema. Through down regulation of PAR-1 expression, the level of MMP-9, TNF-α, IL-1β could be reduced, and oxygen free radical metabolism could be regulated, so as to play the certain protective effects on brain tissue after cerebral hemorrhage.