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机构地区:[1]上海交通大学医学院附属新华医院儿童医学中心小儿外科,200127 [2]上海交通大学医学院附属新华医院营养中心,200127
出 处:《中华小儿外科杂志》2006年第11期588-591,共4页Chinese Journal of Pediatric Surgery
基 金:国家自然科学基金资助项目(编号:30271350)
摘 要:目的研究氧化损伤及肝细胞凋亡在肠外营养(PN)相关肝损害机制中的作用,并探讨中药丹参减轻PN相关肝损害的有效性。方法采用生后6-8 d的新西兰种白兔,体重80-110 g,随机分为3组:①正常对照组(n=10),母乳喂养;②PN组(n=10),持续输注静脉营养液(244)ml·kg-1·d-1)10 d;③PN+丹参组(n=10),在静脉营养液中加人丹参(0.2 ml·kg-1·d-1)。持续静脉营养10d后,分别取血作肝功能生化检测,取肝组织作光镜病理、电镜检查,氧化损伤(丙二醛MDA含量测定)及凋亡细胞(TUNEL法)检测。结果PN组血直接胆红素、胆汁酸均明显高于正常对照组和PN+丹参组(均P<0.05)。肝脏病理显示:PN组可见肝细胞空泡变性、脂肪变性,有多发细胞内淤胆和胆栓形成;PN+丹参组门脉区少量炎细胞浸润,无胆管扩张和胆汁淤积表现;病理学总评分3组分别为:8,22,15,组间两两比较P<0.01。电镜肝细胞细胞器超微结构变化与光镜病理改变相符, PN组可见毛细胆管扩张、微绒毛消失,线粒体肿胀、部分可见脂肪变性,以及早期凋亡表现。MDA检测PN组明显高于对照组(2.04±0.44比1.35±0.29mmol/mgpro,P<0.05)和PN+丹参组(2.04±0.44比1.19±0.14mmol/mgpro,P<0.05)。TUNEL,法检测3组肝细胞凋亡阳性率(%)分别为: 0.92±0.85、44.59±6.68、9.27±7.28,3组两两比较均P<0.01。结论PN可导致新生兔肝细胞出现氧化损伤及凋亡,产生肝损害;而中药丹参可明显减轻PN所致肝细胞损害。Objective To investigate the mechanisms of oxidative injury and apoptosis in PN associated hepatic dysfunction and the possible effectiveness of Danshen (a traditional Chinese medicine) to alleviate this injury. Methods Thirty New Zealand rabbits (6-Sdays old, Wt 80-110g) were divided into 3 groups: 10 in control group (breast fed); 10 in PN group (PN for 10 days); 10 in Danshen + PN group (PN plus Danshen for 10 days). After 10 days, blood biochemistry analysis was performed, the liver histological changes were examined by light scope and electric scope, and the malondialdehyde (MDA) content of liver tissues and TUNEL positive hepatocytes were also determined. Results The serum concentrations of direct bilirubin and bile acid in PN group were significantly higher than those in the control group and Danshen + PN group (P〈0. 05). Compared with the obvious cholestatic changes or hepatic steatosis in the PN group, no obvious cholestatic or steatosis changes could be found in the Danshen + PN group. The histological scores were 8, 22, and 15 in control, PN and PN + Danshen group, respectively. The results of electron microscopy were consistent with the light microscopical findings. MDA value in PN-group was higher than that in the control group (2. 04±0. 44 vs 1.35±0. 29, P〈0. 05) and in the Danshen-PN group (2. 04 ± 0. 44 vs 1. 19 ± 0. 14,P〈0. 05). TUNEL assay showed the positive rate of apoptotic hepatocytes in PN group was the highest among these 3 groups. Conclusions Danshen can reduce hepatocyte apoptosis caused by PN via its' anti-oxidative and anti-apoptotic effects.
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