Ghrelin治疗脑出血大鼠脑水肿及MMP-9表达的影响

目的:研究Ghrelin对大鼠脑出血后脑水肿及脑组织中基质金属蛋白酶-9(MMP-9)表达的影响。方法:选取雄性SD大鼠80只,随机分为对照组(NC组)20只、假手术组(SHAM组)20只、脑出血组(ICH组)20只、Ghrelin治疗组(Ghrelin组)20只。利用自体动脉血注入法建立大鼠脑出血模型;Ghrelin组于建立脑出血模型后经股静脉注射Ghrelin 10 nmol/Kg·d。分别于12 h、24 h、3d、5 d、7 d时间点根据Berderson评分法评估各组大鼠神经系统功能;利用干湿重法测定各组大鼠脑组织含水量;利用蛋白质免疫印迹法(WB)检测脑组织中MMP-9表达情况。结果:在12 h、24 h、3 d、5 d、7 d,ICH组、Ghrelin组大鼠Berderson评分及脑组织含水量高于NC组、SHAM组(P0.05);在5 d、7 d,ICH组大鼠Berderson评分及脑组织含水量高于Ghrelin组(P0.05)。WB结果表明在12 h、24 h、3 d、5 d、7 d,ICH组大鼠脑组织中MMP-9的表达均高于NC组、SHAM组(P0.05);Ghrelin组MMP-9的表达在12 h、24 h、3 d高于NC组、SHAM组(P0.05),在5 d、7 d,与NC组、SHAM组无明显差异(P0.05);在5 d、7 d,ICH组MMP-9表达高于Ghrelin组(P0.05)。结论:在本研究中,Ghrelin可以在5 d后降低脑出血大鼠脑组织中MMP-9的表达程度,从而减轻脑水肿,改善脑出血大鼠神经功能。

Effect of Ghrelin on Expression of MMP-9 and Brain Edema in a Rat Model of Intracerebral Hemorrhage

ABSTRACT Objective: To study the effects of Ghrelin on brain edema and expression of MMP-9 in a rat model of intracerebral hemorrhage. Methods: Eighty male SD rats were randomly divided into NC group(n=20), SHAM group(n=20) , ICH group(n=20) and Ghrelin group(n=20). Experimental intracerebral hemorrhage model was made by injecting autologous caudate artery blood of the rats. Ghrelin group model was made by injecting Ghrelin at a dose of 10 nmol/Kg?d. At 5 observation time(12 h, 24 h, 3 d, 5 d, 7 d), brain functional deficit was evaluated according to Berderson scores. The water content of brain was analyzed by dry/weight measurement. The expression of MMP-9 in brain was detected by Western blotting. Results: Compared with NC group and SHAM group, Berderson scores and water content of brain in ICH group and Ghrelin group were higher at 12 h, 24 h, 3 d, 5 d, 7 d (P<0.05). Compared with ICH group, Berderson scores and water content of brain in Ghrelin group decreased at 5 d, 7 d (P<0.05). The expression of MMP-9 in ICH group was significantly higher than that in NC group and SHAM group (P<0.05) at 12 h, 24 h, 3 d, 5 d, 7 d. Compared with NC group and SHAM group, the expression of MMP-9 in Ghrelin group was higher at 12 h, 24 h, 3 d(P<0.05). The expression of MMP-9 in Ghrelin group was no significant difference with that in NC group and SHAM group at 5 d, 7 d(P>0.05). The expression of MMP-9 in ICH group was higher than that in Ghrelin group (P<0.05) at 5 d, 7 d. Conclusion: In this research, Ghrelin could decrease the expression of MMP-9 in brains of intracerebral hemorrhage rats after 5 d, which contributed to alleviate brain edema and improve the function of nervous system.