枸橼酸莫沙必利对大鼠脑卒中急性期胃肠功能障碍的影响及其机制OACSTPCD
Effect of Mosapride Citrate on gastrointestinal dysfunction in acute stage of stroke rats and its mechanism
目的 探究枸橼酸莫沙必利对大鼠脑卒中急性期胃肠功能障碍的影响,并研究脑卒中急性期胃肠功能障碍与胃肠组织干细胞因子(SCF)/干细胞因子受体(C-kit)通路之间的关系.方法 SD大鼠随机分为正常组、脑卒中组(脑出血组和脑梗死组)、莫沙必利组(脑出血+莫沙必利组和脑梗死+莫沙必利组).采用自体血注入法制备大鼠脑出血模型,采用线栓法制备大鼠大脑中动脉梗死模型.造模成功后,正常组和脑卒中组给予生理盐水灌胃,莫沙必利组给予莫沙必利(0.27 mg/d)灌胃,每天2次,于给药7 d处死大鼠.苏木精-伊红(HE)染色观察大鼠胃肠组织病理变化;RT-PCR法和Western blot法检测SCF、C-kit蛋白及mRNA表达水平.结果 正常组大鼠胃肠细胞清晰、结构完整;脑卒中组大鼠胃肠组织层次紊乱,炎细胞浸润重;莫沙必利组大鼠胃组织细胞变性损伤较脑卒中组大鼠胃肠组织程度减轻.与正常组相比,脑卒中组病理评分显著增高(P<0.05);与脑卒中组比较,莫沙必利组病理评分均显著降低(P<0.05).与正常组相比,脑卒中组SCF、C-kit蛋白及mRNA表达显著降低(P<0.05);与脑梗死组相比,脑出血组胃肠SCF蛋白表达水平显著升高,回肠C-kit蛋白表达显著降低(P<0.05),胃肠组织SCF及C-kit mRNA表达显著升高(P<0.05);相较于脑卒中组,莫沙必利组大鼠胃肠组织SCF、C-kit蛋白及mRNA表达显著升高(P<0.05);脑梗死+莫沙必利组大鼠胃肠组织SCF蛋白表达较脑出血+莫沙必利组显著升高(P<0.05),两组C-kit蛋白表达大致相同(P>0.05).结论 莫沙必利通过上调SCF、C-kit表达,激活SCF/C-kit通路,减轻脑卒中急性期胃肠障碍的发生.
Objective To explore the effect of Mosapride Citrate on gastrointestinal dysfunction in acute stage of stroke in rats and investigate its relationship with SCF/C-kit pathway.Methods SD rats were randomly divided into five groups:normal group,stroke groups(cerebral hemorrhage group,cerebral infarction group),and mosapride groups(cerebral hemorrhage+mosapride group,cerebral infarction+mosapride group).The hemorrhage model was induced by autologous blood injection method,and the infarct model was induced by suture occlusion method.After successful modeling,the rats in normal group and stroke group were given physiological saline by gavage,while the rats in mosapride group were given mosapride(0.27 mg/d)by gavage twice a day.The rats were eutha-nized after seven days of administration.Hematoxylin eosin(HE)was used to observe pathological changes in rat gastrointestinal tissue,RT-PCR and Western blot were used to detect the expression levels of SCF,C-kit protein and mRNA.Results The gastroin-testinal cells in normal group were clear and intact.In stroke group,the gastrointestinal tissue was disordered and the cell infiltration was serious.The degree of gastric tissue degeneration in moxapride group was less than that in stroke group.Compared with normal group,the pathological score was significantly increased in stroke group(P<0.05).Compared with stroke group,the pathological change scores were significantly decreased in moxapride group(P<0.05).Compared with normal group,SCF and C-kit protein and mRNA expressions in stroke group were significantly decreased(P<0.05).Compared with cerebral infarction group,the expression level of gastrointestinal SCF protein was significantly increased in cerebral hemorrhage group(P<0.05),the expression of C-kit protein in ileum was significantly decreased(P<0.05),and the expressions of SCF and C-kit mRNA in gastrointestinal tissue were sig-nificantly increased(P<0.05).Compared with stroke group,the expressions of SCF and C-kit protein and mRNA in gastrointestinal tissue were significantly increased in moxapride group(P<0.05).The expression of SCF protein in gastrointestinal tissue of rats in cerebral infarction+moxapride group was significantly higher than that in cerebral hemorrhage+moxapride group(P<0.05),and the expression of C-kit protein was similar in the two groups(P>0.05).Conclusion Mosapride can activate the SCF/C-kit pathway by upregulating the expression of SCF and C-kit,thereby reducing the occurrence of gastrointestinal disorders in acute stroke.
匡逸;鄢伟;唐明
青岛大学附属青岛市海慈医院(青岛市中医医院)神经内科,青岛 266000青岛大学附属青岛市海慈医院(青岛市中医医院)神经外科
临床医学
枸橼酸莫沙必利脑出血急性期脑梗死急性期胃肠道功能障碍SCF/C-kit通路
Mosapride Citrateacute stage of cerebral hemorrhageacute stage of cerebral infarctiongastrointestinal dysfunc-tionSCF/C-kit pathway
《山西医科大学学报》 2024 (005)
604-609 / 6
青岛市民生科技计划项目(18-6-1-69-nsh)
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