丹参多酚酸盐对实验性肝硬化大鼠肠黏膜屏障功能的改善作用

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (7): 758-763.

丹参多酚酸盐对实验性肝硬化大鼠肠黏膜屏障功能的改善作用

杨丹红^1,2, 叶再元², 何徐军², 张勤³, 周卫民¹, 徐文娟², 吕火祥²

¹浙江中医药大学,杭州 310053, 浙江;
²浙江省人民医院,杭州 310014, 浙江;
³浙江省中医院,杭州310006,浙江

收稿日期:2010-05-10 修回日期:2010-07-11 出版日期:2010-07-26 发布日期:2020-09-15
通讯作者: 叶再元,男,硕士,主任医师,教授,博士生导师,研究方向:胃肠疾病发生机理与防治研究。Tel: 0571-85893001 E-mail: zaiyuanye@163.com
作者简介:杨丹红,女,博士在读,主治医师,从事肝脏疾病药物治疗研究。Tel: 0571-85793819 E-mail: YDH-11@163.com

Improvement effect of salvianolate on small intestinal mucosal barrier in cirrhotic rats

YANG Dan-hong^1,2, YE Zai-yuan², HE Xu-jun², ZHANG Qin³, ZHOU Wei-ming², XU Wen-juan², LV Huo-xiang²

¹Zhejiang Chinese Medical University,Hangzhou 310053,Zhejiang,China;
²Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang,China;
³Zhejiang Hospital of Traditional Chinese Medine,Hangzhou 310006,Zhejiang,China

Received:2010-05-10 Revised:2010-07-11 Online:2010-07-26 Published:2020-09-15

摘要/Abstract

摘要： 目的: 观察丹参多酚酸盐对肝硬化大鼠肠黏膜屏障功能的影响。方法: SD大鼠40%CCl₄-橄榄油溶液建立肝硬化大鼠模型,随机分成4组:模型对照组、丹参多酚酸盐治疗低、中、高剂量组, 每天分别腹腔注射葡萄糖溶液、丹参多酚酸盐12、24、48 mg/kg,持续2周。另取10只大鼠作正常对照。治疗结束后观察各组大鼠死亡率,光度法测定门静脉血清内毒素水平,光镜下观察肠黏膜形态学改变,比较肠黏膜形态学指标,免疫组织化学染色测肠黏膜分泌型免疫球蛋白A(sIgA)染色及积分光密度值变化。结果: 模型对照组大鼠死亡率为42.86%,丹参多酚酸盐高剂量组死亡率为0;各组大鼠门静脉血清内毒素水平模型对照组最高,与其相比,丹参多酚酸盐低剂量组内毒素水平降低(P<0.05),中剂量组与高剂量组显著降低(P<0.01)。模型对照组回肠绒毛萎缩、脱落、断裂,黏膜变薄,治疗组肠黏膜逐渐修复,绒毛变整齐,绒毛高度、黏膜、全层厚度比模型对照组增长、变厚(P<0.01)。模型对照组sIgA免疫组化信号表达弱,治疗组染色表达增强。模型对照组积分光密度值最低,中剂量治疗组升高(P>0.05),高剂量组显著升高(P<0.01)。结论: 丹参多酚酸盐能降低肝硬化大鼠门静脉血内毒素水平,促进肠黏膜上皮结构损伤恢复,保持形态完整,增强黏膜局部免疫功能。

关键词: 丹参多酚酸盐, 肝硬化, 内毒素, 肠黏膜, 分泌型免疫球蛋白A

Abstract: AIM: To investigate the effect of salvianolate on small intestinal mucosal barrier in rats with CCl₄-induced liver cirrhosis.METHODS: Cirrhosis was induced in rats using CCl₄ (0.3 mL/kg ). Rats were divided randomly into four groups:untreatmeat, low-dose salvianolate(12 mg/kg), medium-dose salvianolate(24 mg/kg), and high-dose salvianolate(48 mg/kg). They were all treated for 2 weeks.Another 10 healthy rats were enrolled as normal control. Mortality of cirrhotic rats in each group were evaluated after treatment. Serum samples were collected from the portal vein for the detection of endotoxin. Tissue samples from the ileocecum were observed under light microscopy for morphological changes.A contrasting study on the expression of secretary immunoglobulin A(sIgA) were performed in each group by immunohistochemical staining method.RESULTS: The mortality of cirrhotic rats in the untreatmeat group was 42.86%. No cirrhotic rat died in the high-dose salvianolate group. The serum endotoxin level was highter in the untreatmeat group than that in salvianolate group(P<0.05). Intestinal mucosal and villous atrophy were observed in the untreatmeat group, with necrosis and shedding of the intestinal mucosal epithelium. These pathological changes were reversed in the salvianolate-treated groups.The expression of sIgA in intestinal mucosa were reduced obviously in the untreatmeat group, in compared with those in the salvianolate-treated groups and healthy rats group. The integral optical density of immunohistochemical staining image in untreatmeat group was obviously lower than that in high-dose salvianolate-treated group (P<0.01). CONCLUSION: Salvianolate is helpful for reducing endotoxin level,ameliorating injury of intestinal mucosa,enhancing immune function of intestinal mucosa in rats with CCl₄ induced cirrhosis,and therefore improving the barrier function of intestinal mucosa.

Key words: Salvianolate, Cirrhosis, Endotoxin, Intestinal mucosa, sIgA

中图分类号:

R965.2

杨丹红, 叶再元, 何徐军, 张勤, 周卫民, 徐文娟, 吕火祥. 丹参多酚酸盐对实验性肝硬化大鼠肠黏膜屏障功能的改善作用[J]. 中国临床药理学与治疗学, 2010, 15(7): 758-763.

YANG Dan-hong, YE Zai-yuan, HE Xu-jun, ZHANG Qin, ZHOU Wei-ming, XU Wen-juan, LV Huo-xiang. Improvement effect of salvianolate on small intestinal mucosal barrier in cirrhotic rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(7): 758-763.

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