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作 者:黄品婕[1] 李晓芸[1] 罗晨芳[1] 张瑷兰[1] 刘健培
机构地区:[1]中山大学附属第三医院麻醉科 [2]胃肠外科,广东广州510630
出 处:《中国病理生理杂志》2014年第1期85-90,共6页Chinese Journal of Pathophysiology
基 金:广东省医学科学基金资助项目(No.B2012123);广东省自然科学基金博士启动项目(No.S2013040016160)
摘 要:目的:探讨肠缺血后再灌注前干预肥大细胞功能对SD大鼠继发肝脏损伤的影响及机制。方法:35只大鼠随机分成5组:假手术组(S组)、缺血再灌注组(IR组)、缺血再灌注+色甘酸钠组(IR+C组)、缺血再灌注+酮替芬组(IR+K组)和缺血再灌注+compound 48/80组(IR+CP组)。复制大鼠肠缺血再灌注模型,IR+C、IR+K和IR+CP组分别在再灌注前5 min经尾静脉给予相应药物,S和IR组给予等量生理盐水。再灌注4 h后处死大鼠,观察各组肝脏病理变化及评分,测定血清丙氨酸氨基转移酶(ALT)活性、天冬氨酸氨基转移酶(AST)活性和组胺含量,检测肝脏乳酸脱氢酶(LDH)活性、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性和肿瘤坏死因子α(TNF-α)、白细胞介素8(IL-8)水平。结果:与S组相比,IR组肝脏病理损伤明显(P<0.05),血清ALT、AST水平、组胺含量、肝LDH活性、MDA、TNF-α、IL-8水平升高,SOD活性减弱(P<0.05)。与IR组相比,IR+C和IR+K组肝脏损伤减轻,以上指标呈相反趋势(P<0.05),IR+CP组则加重肝损伤及恶化检测结果(P<0.05)。结论:再灌注前抑制肥大细胞功能可以减轻肠缺血再灌注后早期肝脏损伤,其机制可能与组胺释放、氧化损伤和炎症反应有关。AIM. To explore the effect of intervention for mast cell function before reperfusion on intestinal is- chemia-reperfusion (IR)-induced early liver injury. METHODS: Adult SD rats (n = 35 ) were randomized into 5 groups with 7 rats each t sham operation group ( S group), IR group, cromolyn sodium treatment group ( IR + C group, 25 mg/ kg), ketotifen treatment group (IR + K group, 1 mg/kg), compound 48/80 treatment group (IR + CP group, 0.75 mg/ kg), IR was induced by superior mesenteric artery occlusion for 75 min followed by 4 h of reperfusion. The agents were in- travenously administered 5 rain before reperfusion. The serum levels of aspartate aminotransferase ( AST), alanine amin- otransferase (ALT) and histamine, and the liver levels of lactate dehydrogenase (LDH), tumor necrosis factor ot (TNF- or), interleukin-8 (IL-8), malondialdehyde (MDA) and superoxide dismutase (SOD) were assessed. The liver his- topathologic changes were also evaluated. RESULTS: IR resulted in severe liver injury as demonstrated by great increases in injury scores, concomitant significant increases in serum levels of AST, ALT and histamine, and liver levels of LDH, TNF-ct, IL-8, and MDA, accompanied by reduced SOD activity (all P 〈 0.05 vs S group). Treatment with cromolyn sodi- um or ketotifen markedly alleviated IR-mediated liver injury as confirmed by significant reduction of the above biomedical changes, whereas compound 48/80 further aggravated liver injury by dramatically enhancing the biomedical changes ( all P 〈0.05 vs IR group). CONCLUSION: Inhibition of mast cell function before reperfusion may reduce early liver injury in- duced by intestinal ischemia reperfusion. Histamine, oxidative stress and inflammatory response may provide promising effects on it.
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