从慢传输型便秘大鼠结肠c-kit /SCF的基因表达及神经传导通路探讨六磨汤的调节机制

Slow-transit constipation rat colon muscle between cluster Cajal interstitial cells (interstitial cells of Cajal, ICC)is a kind of special interstitial cells of gastrointestinal nervous system, which is non nerve but related closely with nerve, is the pacemaker cells of intestinal slow wave ,and plays an important role in intestinal neural signal transfer; moreover, its distribution and disorderly network is pathological basis of slow-transit constipation, in addition, the cell membrane can express c-kit protein specifically, which is a kind of transmembrane glycoprotein. The signal path started by unity of c-kit and its ligands stem cell factor (SCF) plays an important role for ICC development, differentiation and phenotype maintaining.Abnormal expression of c-kit, SCF genes and the corresponding signal paths damaged can cause ICC phenotypic change, resulting in form and function abnormal.C-kit and SCF protein expression decline significantly in patients'colon with slow-transit constipation.Liumo Decoction is frequently-used and effective prescription for treatment of slow-transit constipation, this topic explores the mechanism of Liumo Decoction from c-kit/SCF gene expression and neural pathway for treatment of slow-transit constipation.

慢传输型便秘大鼠结肠肌间丛Cajal间质细胞(interstitial cells of Cajal,ICC) 是胃肠道神经系统的一种非神经但又与神经密切相关的特殊间质细胞，是肠道慢波的起搏细胞，并在肠神经信号传递中起重要作用，其分布和网络的杂乱性是慢传输型便秘的病理基础，其细胞膜可特异性表达一种跨膜糖蛋白c-kit蛋白。c-kit与其配体干细胞因子(SCF)结合所启动的信号通路，对ICC的发育、分化及表型维持至关重要。 c-kit ,SCF基因异常表达及相应的信号通路受损可引起ICC表型发生转化，导致形态和功能异常。慢传输型便秘(slow transit constipation, STC)患者结肠存在c-kit和SCF蛋白表达的显著下降。六磨汤为治疗慢传输型便秘的常用有效方剂，本课题从c-kit/SCF基因表达及神经传导通路探讨六磨汤治疗慢传输型便秘的机制。

慢传输型便秘患者结肠存在c-kit/SCF基因表达及神经传导通路传导异常。六磨汤为治疗慢传输型便秘的有效方剂。本课题通过给大鼠饲喂含复方苯乙哌啶的饲料进行造模，然后进行活性炭灌胃，测定首粒黑便排出时间，确定成功建立大鼠模型后，进行随机分组对照实验。对治疗后各组大鼠分别进行肠道传输功能测定、结肠肌电测定、结肠神经病理学检测、Real time PCR分析，从c-kit/SCF基因表达及神经传导通路探讨六磨汤治疗慢传输型便秘的机制。结果：六磨汤能够显著调节造模药物对慢传输型便秘大鼠结肠肌电慢波频率紊乱，振幅增大，频率及振幅的变异系数显著增高和神经节数量减少及纤维增生等影响。六磨汤通过提高c-kit mRNA相对含量、SCF mRNA相对含量，来治疗慢传输型便秘的。项目资助发表论文9篇，其中1篇在SCI期刊发表。获得专利1项，申请2项。培养3名硕士生,皆在读。成功举办国内学术会议1次。项目投入经费48万元，支出46.8394万元，支出基本与预算相符。剩余经费1.1606万元，剩余经费计划用于本项目研究后续论文发表所用。