Effect of Berberine from Coptis chinensis on Apoptosis of Intestinal Epithelial Cells in a Mouse Model of Ulcerative Colitis: Role of Endoplasmic Reticulum Stress
Effect of Berberine from Coptis chinensis on Apoptosis of Intestinal Epithelial Cells in a Mouse Model of Ulcerative Colitis: Role of Endoplasmic Reticulum Stress
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DOI：
10.1155/2020/3784671
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发表时间：
2020-04
期刊：
影响因子：
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通讯作者：
Shen Yan;Li Yingchao;Wang Zhangliu;Ruan Xianli;Lili Si;Ni Siyi;Zhong Jihong
中科院分区：
文献类型：
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作者：
Shen Yan;Li Yingchao;Wang Zhangliu;Ruan Xianli;Lili Si;Ni Siyi;Zhong Jihong
本研究旨在验证黄连素(BBR)对溃疡性结肠炎(UC)小鼠内质网应激(ERS)和肠上皮细胞(IECS)凋亡的影响。将BALB/c小鼠随机分为5组：空白对照组、模型组、补肾活血方低、中、高剂量组。建立葡聚糖硫酸钠(DSS)诱导的大鼠UC模型，低、中、高剂量BBR组同时灌胃BBR混悬液7d，末次给药后测定疾病活动指数(DAI)和结肠组织损伤指数(TDI)。TUNEL法检测IECs的凋亡率。免疫组织化学和/或实时定量聚合酶链式反应检测GRP78、caspase-12和caspase-3的表达。在BBR治疗组中，结肠炎的临床症状和组织病理学损害均显著减轻。补肾活血方高剂量组DAI(0.48±0.36)和TDI(1.62±0.64)较模型组(1.50±0.65和3.88±0.04)均显著降低(P<0.01)。模型组大鼠结肠组织中凋亡的IECs数量明显增加，GRP78、caspase-12、caspase-3蛋白表达显著增加，GRP78mRNA表达上调。补肾活血方低、中、高剂量组的IECs凋亡数明显减少。补肾活血方中、高剂量组GRP78和caspase-3表达水平显著降低，补肾活血方高剂量组caspase-12表达显著降低，补肾活血方高剂量组GRP78基因表达水平显著降低。补肾活血方能有效降低UC小鼠肠上皮细胞凋亡率，减轻结肠炎症反应。其潜在机制可能涉及ERS调控和抑制ERS介导的caspase-12/caspase-3凋亡信号通路的激活。
The purpose of this study was to verify the effect of berberine (BBR) on endoplasmic reticulum stress (ERS) and apoptosis of intestinal epithelial cells (IECs) in mice with ulcerative colitis (UC). BALB/c mice were randomly divided into five groups as follows: blank control, model, and low-, medium-, and high-dose BBR. A dextran sodium sulfate- (DSS-) induced model of UC was prepared, and the low-, medium-, and high-dose BBR groups were simultaneously gavaged with a BBR suspension for 7 d. Disease activity index (DAI) was assessed, and tissue damage index (TDI) was assessed from colon samples after the last administration. TUNEL assays were used to detect apoptosis of IECs. Immunohistochemistry and/or real-time PCR were applied to determine the expression of GRP78, caspase-12, and caspase-3. In all BBR treatment groups, clinical symptoms of colitis and histopathological damage were significantly reduced. The high-dose BBR group exhibited particularly pronounced decrease (p < 0.01) in both DAI (0.48 ± 0.36) and TDI (1.62 ± 0.64) relative to the model group (1.50 ± 0.65 and 3.88 ± 0.04, respectively). In colon tissues of the model group, the number of apoptotic IECs was significantly increased; the expression of GRP78, caspase-12, and caspase-3 proteins was significantly increased; and the expression of the GRP78 mRNA was upregulated. In low-, medium-, and high-dose BBR groups, the number of apoptotic IECs was significantly reduced. Moreover, GRP78 and caspase-3 expression levels were significantly decreased in the medium- and high-dose BBR groups, caspase-12 expression was significantly decreased in the high-dose BBR group, and the GRP78 mRNA expression level was significantly decreased in the high-dose BBR group. BBR can effectively reduce the rate of IEC apoptosis in UC mice and alleviate the inflammatory response in the colon. The underlying mechanism seems to involve ERS modulation and inhibition of ERS-mediated activation of the caspase-12/caspase-3 apoptosis signaling pathway.