摘要
目的探讨白术七物颗粒抑制Cajal间质细胞(ICC)凋亡治疗慢传输型便秘(STC)的作用机制。方法利用洛哌丁胺复制STC小鼠模型,将其随机分成对照组,模型组,白术七物颗粒低、中、高剂量组和普芦卡必利组,另设对照组。白术七物颗粒低、中、高剂量组分别灌以不同浓度白术七物颗粒,普芦卡必利组灌以普芦卡必利,对照组与模型组灌胃等体积蒸馏水。HE染色观察结肠组织病理变化,IHC法检测结肠c-kit表达,TUNEL法检测结肠ICC凋亡,WB法检测结肠PI3K、AKT、mTOR蛋白表达。结果与对照组相比,模型组结肠组织结构破坏,c-kit表达显著降低,ICC凋亡显著升高,p-PI3K/PI3K、p-AKT/AKT、p-mTOR/mTOR水平显著升高(P<0.01)。与模型组相比,白术七物颗粒各剂量组及普芦卡必利组结肠组织结构改善,白术七物颗粒高剂量组及普芦卡必利组c-kit表达显著升高,白术七物颗粒各剂量组及普芦卡必利组ICC凋亡显著降低,白术七物颗粒低剂量组p-PI3K/PI3K、p-AKT/AKT水平降低,白术七物颗粒中、高剂量组及普芦卡必利组p-PI3K/PI3K、p-AKT/AKT、p-mTOR/mTOR水平显著降低(P<0.05,P<0.01)。与白术七物颗粒高剂量组相比,白术七物颗粒低剂量组c-kit表达降低,白术七物颗粒低、中剂量组p-PI3K/PI3K水平显著升高,普芦卡必利组p-AKT/AKT水平降低(P<0.05,P<0.01)。结论白术七物颗粒可有效改善STC小鼠结肠组织损伤,促进c-kit表达,抑制ICC凋亡,其作用机制可能与PI3K/Akt/mTOR信号通路有关。
Objective To explore the mechanism of Baizhu Qiwu Granules(白术七物颗粒)on inhibiting the apoptosis of Cajal interstitial cells(ICC)in the treatment of slow transit constipation(STC).Methods The STC mouse model was replicated with loperamide and randomly divided into control group,model group,Baizhu Qiwu Granules low-dose,medium-dose and high-dose groups and prucalopride group,and another control group was set up.The low-dose,medium-dose and highdose of Baizhu Qiwu Granules groups were respectively given different concentrations of Baizhu Qiwu Granules,the prucalopride group was given prucalopride,and the control group and the model group were given the same volume of distilled water.The pathological changes of colon tissue were observed by HE staining,the expression of colon c-kit was detected by IHC method,the apoptosis of colonic ICC was detected by TUNEL method,and the protein expressions of PI3K,AKT and mTOR in colon were detected by WB method.Results Compared with the control group,the colon tissue structure was destroyed in the model group,the expression of c-kit was significantly decreased,the apoptosis of ICC was significantly increased,and the levels of p-PI3K/PI3K,p-AKT/AKT,and p-mTOR/mTOR were significantly increased(P<0.01).Compared with the model group,the colon tissue structure in each dose group of Baizhu Qiwu Granules and the prucalopride group improved,the expression of c-kit in the high dose group of Baizhu Qiwu Granules and the prucalopride group was significantly increased,and the expression of c-kit in the Baizhu Qiwu Granules group and the prucalopride group was significantly increased.The ICC apoptosis was significantly decreased in each dose group of granule and prucalopride group.The levels of p-PI3K/PI3K and p-AKT/AKT in the low-dose Baizhu Qiwu Granules group were decreased,and the levels of p-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR were significantly decreased in Baizhu Qiwu Granules medium-dose and high-dose groups and prucalopride group(P<0.05,P<0.01).Compared with the high-dose group of Baizhu Qiwu Granules,the expression of c-kit in the low-dose group of Baizhu Qiwu Granules decreased,and the expression levels of p-PI3K/PI3K in the low-dose and medium-dose groups of Baizhu Qiwu Granules were significantly increased,and the level of p-AKT/AKT decreased in the prucalopride group(P<0.05,P<0.01).Conclusion Baizhu Qiwu Granules can effectively improve colon tissue damage in STC mice,promote the expression of c-kit,and inhibit the apoptosis of ICC,and its mechanism may be related to the PI3K/Akt/mTOR signaling pathway.
作者
林仁敬
郭夏君
王梨力
罗雯鹏
李帅军
罗敏
肖金银
LIN Renjing;GUO Xiajun;WANG Lili;LUO Wenpeng;LI Shuaijun;LUO Min;XIAO Jinyin(The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine,Changsha 410005,Hunan,China;Hunan University of Traditional Chinese Medicine,Changsha 410208,Hunan,China)
出处
《辽宁中医药大学学报》
CAS
2023年第8期5-9,F0003,共6页
Journal of Liaoning University of Traditional Chinese Medicine
基金
湖南省自然科学基金项目(2021JJ30517)
湖南省中医药科研计划项目(2021063)
湖南中医药大学校级科研联合基金项目(2020XJJJ051)
湖南省中医药防治肛肠疾病重点研究室项目[湘中医药函(2020)51号]。
