Department of Infection, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang Province, China.
World J Gastroenterol. 2012 Dec 21;18(47):7040-7. doi: 10.3748/wjg.v18.i47.7040.
To study the effect of salvianolate on tight junctions (TJs) and zonula occludens protein 1 (ZO-1) in small intestinal mucosa of cirrhotic rats.
Cirrhosis was induced using carbon tetrachloride. Rats were randomly divided into the untreated group, low-dose salvianolate (12 mg/kg) treatment group, medium-dose salvianolate (24 mg/kg) treatment group, and high-dose salvianolate (48 mg/kg) treatment group, and were treated for 2 wk. Another 10 healthy rats served as the normal control group. Histological changes in liver tissue samples were observed under a light microscope. We evaluated morphologic indices of ileal mucosa including intestinal villi width and thickness of mucosa and intestinal wall using a pathological image analysis system. Ultrastructural changes in small intestinal mucosa were investigated in the five groups using transmission electron microscopy. The changes in ZO-1 expression, a tight junction protein, were analyzed by immunocytochemistry. The staining index was calculated as the product of the staining intensity score and the proportion of positive cells.
In the untreated group, hepatocytes showed a disordered arrangement, fatty degeneration was extensive, swelling was obvious, and disorganized lobules were divided by collagen fibers in hepatic tissue, which were partly improved in the salvianolate treated groups. In the untreated group, abundant lymphocytes infiltrated the fibrous tissue with proliferation of bile ducts, and collagen fibers gradually decreased and damaged hepatic lobules were partly repaired following salvianolate treatment. Compared with the untreated group, no differences in intestinal villi width between the five groups were observed. The villi height as well as mucosa and intestinal wall thickness gradually thickened with salvianolate treatment and were significantly shorter in the untreated group compared with those in the salvianolate treatment groups and normal group (P < 0.01). The number of microvilli decreased and showed irregular lengths and arrangements in the untreated group. The intercellular space between epithelial cells was wider. The TJs were discontinuous, which indicated disruption in TJ morphology in the untreated group. In the treated groups, the microvilli in the intestinal epithelium were regular and the TJs were gradually integrated and distinct. The expression of ZO-1 decreased in the small intestine of the untreated cirrhotic rats. The high expression rate of ZO-1 in ileal mucosa in the untreated group was significantly lower than that in the medium-dose salvianolate group (21.43% vs 64.29%, χ(2) = 5.25, P < 0.05), high-dose salvianolate group (21.43% vs 76.92%, χ(2) = 8.315, P < 0.01) and normal group (21.43% vs 90%, χ(2) = 10.98, P < 0.01).
Salvianolate improves liver histopathological changes, repairs intestinal mucosa and TJ structure, and enhances ZO-1 expression in the small intestinal mucosa in cirrhotic rats.
研究丹参多酚酸盐对肝硬化大鼠小肠黏膜紧密连接（TJ）和闭合蛋白 1（ZO-1）的影响。
采用四氯化碳诱导肝硬化。大鼠随机分为未治疗组、低剂量丹参多酚酸盐（12 mg/kg）治疗组、中剂量丹参多酚酸盐（24 mg/kg）治疗组和高剂量丹参多酚酸盐（48 mg/kg）治疗组，治疗 2 周。另取 10 只健康大鼠作为正常对照组。光镜下观察肝组织学变化。采用病理图像分析系统评价回肠黏膜的形态学指标，包括肠绒毛宽度、黏膜和肠壁厚度。采用透射电镜观察 5 组大鼠小肠黏膜的超微结构变化。免疫细胞化学法分析紧密连接蛋白 ZO-1 的表达变化。染色指数计算为染色强度评分与阳性细胞比例的乘积。
未治疗组肝细胞排列紊乱，脂肪变性广泛，肿胀明显，肝组织内胶原纤维分隔不整齐的肝小叶，丹参多酚酸盐治疗组部分改善。未治疗组大量淋巴细胞浸润纤维组织，胆管增生，胶原纤维逐渐减少，受损肝小叶部分修复。与未治疗组相比，5 组间肠绒毛宽度无差异。随着丹参多酚酸盐的治疗，绒毛高度以及黏膜和肠壁厚度逐渐增厚，未治疗组明显短于丹参多酚酸盐治疗组和正常组（P<0.01）。未治疗组肠上皮细胞的微绒毛减少，排列不规则，细胞间间隙增宽，TJ 形态不连续。治疗组肠上皮细胞微绒毛规则，TJ 逐渐融合，形态清晰。未治疗的肝硬化大鼠小肠ZO-1 表达减少。未治疗组回肠黏膜ZO-1 高表达率明显低于中剂量丹参多酚酸盐组（21.43%比 64.29%，χ²=5.25，P<0.05）、高剂量丹参多酚酸盐组（21.43%比 76.92%，χ²=8.315，P<0.01）和正常组（21.43%比 90%，χ²=10.98，P<0.01）。
丹参多酚酸盐可改善肝硬化大鼠的肝组织病理学变化，修复小肠黏膜和 TJ 结构，增强肝硬化大鼠小肠黏膜ZO-1 的表达。
