汉防己甲素对小鼠溃疡性结肠炎的作用机制研究

Effects and mechanism of tetrandrine on the ulcerative colitis in mice

目的探讨汉防己甲素对恶唑酮诱导的小鼠溃疡性结肠炎(UC)的影响及其机制。方法按照体重将雌性BALB/c小鼠随机均分为4组:空白组、模型组、对照组和实验组,每组10只。除空白组外,其余3组均给予恶唑酮灌肠制备UC模型。空白组和模型组小鼠给予0.9%NaCl,对照组给予柳氮磺吡啶肠溶片(0.5 g·kg^-1溶于0.9%NaCl)灌胃,实验组给予汉防己甲素(40 mg·kg^-1溶于0.9%NaCl)灌胃。对各组小鼠结肠进行组织学损伤指数(HI)评分,用免疫组化染色检测小鼠结肠核因子kappa B(NF-κB) p65、肿瘤坏死因子-α(TNF-α)和紧密连接蛋白闭合蛋白(occludin)的表达(灰度值)。结果空白组、模型组、对照组和实验组的小鼠结肠HI评分分别为0.73±0.52,22.70±1.88,12.08±1.22和12.30±0.92;这4组的小鼠结肠NF-кB p65表达水平分别为175.80±2.82,149.82±0.58,164.92±0.99和163.65±2.02;这4组的TNF-α表达水平分别为156.79±1.53,110.15±2.40,141.84±1.30和143.34±1.47;这4组的occludin表达水平分别为101.73±2.14,138.49±1.59,126.37±2.03和127.61±1.70。上述指标:模型组与空白组比较,差异均有统计学意义(均P<0.05);实验组和对照组与模型组相比,均有统计学意义(均P<0.05),表明汉防己甲素的疗效与柳氮磺吡啶肠溶片相当。结论汉防己甲素能够减轻UC的炎症反应,从而改善UC的肠道病变,提高UC的黏膜屏障功能。

Objective To investigate the effect and mechanism of tetrandrine on oxazolone-induced ulcerative colitis(UC) in mice. Methods Mice were randomly divided into 4 groups(n=10): Blank group, model group, control group, experimental group. Except the mice in blank group,the other three groups were given oxazolone to prepare UC model. The mice in the blank group and the model group were given normal saline. The control group was given sulfasalazine(0.5 g·kg^-1 dissolved in 0.9%NaCl), and the experimental group was given tetrandrine(40 mg·kg^-1 dissolved in 0.9%NaCl) by stomach. The histological index(HI) of the colon of mice was scored. The expression(gray level) of nuclear factor kappa-B(NF-кB) p65,tumor necrosis factor-α(TNF-α) and occludin in the colon of mice was detected by immunohistochemical staining. Results The colon HI scores in blank group, model group, control group and experimental group were 0.73±0.52, 22.70±1.88, 12.08±1.22 and 12.30±0.92;the expression of NF-κB p65 protein in the four group were 175. 80 ± 2. 82,149. 82 ± 0. 58,164. 92 ± 0. 99 and163. 65 ± 2. 02;the expression of TNF-α protein in the four group were 156. 79 ± 1. 53,110. 15 ± 2. 40,141. 84 ± 1. 30 and 143. 34 ± 1. 47;the expression of occludin protein in the four group were 101. 73 ± 2. 14,138. 49 ± 1. 59,126. 37 ± 2. 03 and 127. 61 ± 1. 70. Comparison between model group and blank group, the differences of the indexes were statistically significant(all P < 0. 05);comparison between control group,experimental group and model group,the differences of the indexes were statistically significant(all P < 0. 05). It was indicated that the efficacy of tetrandrine was similar to sulfasalazine. Conclusion Tetrandrine could reduce the inflammatory response of UC,improve the intestinal lesions of UC,and enhance the mucosal barrier function of UC.