黄连总碱对乙醇致大鼠胃粘膜损伤的保护作用及其机制研究

摘要

目的:研究黄连总碱(TA)对乙醇致大鼠胃粘膜损伤的保护作用机制.方法:建立乙醇致胃粘膜损伤动物模型,通过胃粘膜损伤指数和病理学改变来观察TA的保护作用.检测胃粘膜一氧化氮(NO)、丙二醛(MDA)和活性氧(·OH)的含量以及超氧化物歧化酶(SOD)的活力.免疫组织化学方法分析神经型一氧化氮合成酶(nNOS)、内皮型NOS(eNOS)和诱导型NOS(iNOS)在胃粘膜的表达.结果:TA剂量依赖性地抑制乙醇致大鼠胃粘膜损伤,且作用强于等量的小檗碱(Ber).TA明显阻遏乙醇引起的胃粘膜MDA、·OH升高以及NO、SOD降低.TA抑制乙醇所致的nNOS、eNOS在胃粘膜表达降低以及iNOS过表达.结论:黄连能抗人类酒精性胃粘膜损伤,该作用是各生物碱相互增效的结果.作用机制涉及:抑制氧自由基产生;促进自由基清除;减轻脂质过氧化;阻遏nNOS、eNOS表达降低以及iNOS过表达,维持胃粘膜的NO含量在正常水平.%AIM: This study aimed at investigating the effects and mechanism of total alkaloids from Rhizoma Coptidis (TA) on ethanol-induced gastric mucosal injury in rats. METHODS: The experimental gastric damages were established by intragastric ethanol, and the protective effects of TA were evaluated by calculating lesion indices contents and superoxide dismutase (SOD) activity from rat gastric mucosa were measured to explore the interrelation between therapeutic effects of TA and these factors. The expressions of neuronal nitrogen monoxide synthase (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS)from ethanol-damaged gastric mucosa in rats were analysised using immunohistochemical method. RESULTS: TA significantly inhibited the gastric injury induced by ethanol ,in dose-dependent manner,and the effect of TA was superior to that of Berberine (Ber). TA obviously antric mucosa. TA significantly suppressed ethanol-induced decreasing nNOS and eNOS expression and elevation of iNOS expression in rat gastric mucosa. CONCLUSION: Rhizoma Coptidis is a potent candidate in therapeutic drugs of human alcohol-induced gastric injury. Its anti-injury effects involve in Ber and other ingredients of TA. The protective mechanisms of TA involve in inhibiting generation of oxygen-derived free radical, accelerating scavenging of free radicals, relieving lipid peroxidation, and maintaining NO content in normal level by inhibiting decreasing of nNOS and eNOS expression and elevation of iNOS expression.