郑舒泽,郭强,张贵民,潘丽红,曾克武
ZHENG Shu-ze,GUO Qiang,ZHANG Gui-min,PAN Li-hong,ZENG Ke-wu

• 1:北京大学药学院天然药物及仿生药物国家重点实验室
• 2:鲁南制药集团股份有限公司中药制药共性技术国家重点实验室

摘要(Abstract)：

研究首荟通便胶囊对盐酸洛哌丁胺所致的慢传输型便秘小鼠的治疗作用及潜在机制。以盐酸洛哌丁胺诱导ICR小鼠作为慢传输型便秘模型,将50只ICR小鼠分为空白组、模型组以及首荟通便胶囊提取物高、中、低剂量(100,200,400 mg·kg~(-1))组,然后模型组及给药组利用盐酸洛哌丁胺灌胃的方法造模使小鼠获得慢传输型便秘。造模成功后,各给药组分别以高、中、低剂量灌胃给药。给药14 d后,测量首次排便时间、6 h排便粒数、6 h排便湿重及干重、6 h内排黑便数量及粪便含水量。取肠道组织进行c-Kit和干细胞因子(stem cell factor, SCF)免疫组化切片检测空白组、模型组以及首荟通便胶囊提取物高、中、低剂量组c-Kit和SCF表达情况,HE染色法检测小鼠肠道内壁组织变化。同时取部分肠道组织检测小鼠肠道组织三磷酸腺苷(ATP)合成酶和异柠檬酸脱氢酶活性。结果显示,首荟通便胶囊可以有效改善盐酸洛哌丁胺诱导的ICR小鼠慢传输型便秘症状,促进肠道运动。首荟通便胶囊能明显缩短慢传输型便秘模型小鼠首粒黑便排出时间,提高肠道推进率、粪便含水量及数量,改善便秘症状,其作用机制可能与提高肠道组织ATP合成酶活性、线粒体异柠檬酸脱氢酶活性,上调c-Kit/SCF信号通路,促进Cajal间质细胞增殖,增强肠道神经传递以及肠道动力有关。
Shouhui Tongbian Capsules was used to explore the therapeutic effect and potential mechanism on slow transit constipation model mice induced by loperamide hydrochloride. In the experiment, loperamide hydrochloride-induced ICR mice were used as the model of slow transit constipation. Fifty ICR mice were divided into the blank group, model group and high, medium and low dose groups of Shouhui Tongbian Capsules extract(100, 200 and 400 mg·kg~(-1)). The model group and the administration groups were then modeled using loperamide hydrochloride intragastrically to obtain slow transit constipation. After successful modeling, high, medium and low doses of drugs were given to each drug group by intragastric administration. After 14 days of administration, the first defecation time, 6 h defecation grain number, 6 h defecation wet weight and dry weight, black feces discharged within 6 h and the fecal water content were measured. Intestinal tissues were taken for c-Kit and SCF immunohistochemical sections to detect the expression of c-Kit and SCF in the blank group, model group and high, medium and low dose groups of the medicinal extract of Shouhui Tongbian Capsules. The tissue changes in the intestinal wall of mice were detected by HE staining. At the same time, partial intestinal tissues were taken to test the activity of ATP synthase and isocitrate dehydrogenase in intestinal tissues of mice. Results showed that Shouhui Tongbian Capsules effectively improved the symptoms of slow transit constipation in ICR mice and promoted intestinal movement. Shouhui Tongbian Capsules obviously shortened the time of discharging black stool for the first time, improved the intestinal propulsion rate, increased the water content and amount of feces, and improved the constipation symptoms. Mechanism study revealed that Shouhui Tongbian Capsules increased ATP synthase activity and mitochondrial isocitrate dehydrogenase activity in intestinal tissue, and up-regulated c-Kit/SCF signaling pathway to promote interstitial Cajal cells proliferation, intestinal nerve transmission, intestinal motility and transport capacity.

关键词(KeyWords)： 消化系统疾病;慢传输型便秘;首荟通便胶囊;线粒体异柠檬酸脱氢酶;c-Kit/SCF通路
diseases of digestive system;slow transit constipation;Shouhui Tongbian Capsules;mitochondrial isocitrate dehydrogenase;c-Kit/SCF pathway

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81973505,81773932)

作者(Author): 郑舒泽,郭强,张贵民,潘丽红,曾克武
ZHENG Shu-ze,GUO Qiang,ZHANG Gui-min,PAN Li-hong,ZENG Ke-wu

DOI: 10.19540/j.cnki.cjcmm.20201125.401

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