蜜炙远志调控胃肠Cajal间质细胞及其关联机制的研究
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摘要
目的意义：探索蜜炙远志调控胃肠Cajal间质细胞改善胃肠动力障碍的关联机制。从分子水平揭示蜜炙缓解远志胃肠靶器官毒性的科学内涵,以指导临床安全、合理使用远志,故本研究具有重要的学术意义和实用价值。
方法：应用胃肠电生理学、分子生物学、免疫组织化学等方法和手段,探索蜜炙远志调控胃肠Cajal细胞及其关联机制。①采用BL-420生物机能实验系统,考察了对大鼠胃、肠电慢波的影响。②采用免疫组化方法,考察了对大鼠胃、小肠肌间神经丛c-kit阳性ICC细胞的影响。③采用RT-PCR法,考察了对大鼠胃和小肠c-kit、SCFmRNA表达水平的影响。④采用Western Blot法,考察了对大鼠胃和小肠c-kit、SCF蛋白表达水平的影响。⑤采用HE染色,观察了对大鼠胃和小肠组织形态的影响。⑥采用TUNEL法,观察了对大鼠胃和小肠组织细胞凋亡的影响。
结果：①生远志组能显著抑制胃电慢波振幅(P<0.05),其胃、小肠电慢波频率变异系数显著升高(P<0.01)。蜜远志组对胃和小肠电慢波频率、振幅无显著影响(P>0.05)；对胃和小肠电慢波频率变异系数、慢波振幅变异系数也无显著影响(P>0.05)。远志总皂苷组能显著抑制胃电振幅和小肠电慢波频率(P<0.01,P<0.05)；胃及小肠电慢波频率变异系数和慢波振幅变异系数显著增高(P<0.01)。②生远志组和总皂苷组能显著降低胃、小肠肌间神经丛c-kit阳性ICC细胞的含量(P<0.01)；而蜜远志组对胃、小肠肌间神经丛c-kit阳性ICC含量无显著影响(P>0.05)。③生远志组和远志总皂苷组能显著降低大鼠胃窦区、小肠组织中c-kit、SCFmRNA和蛋白的表达水平(P<0.01)；蜜远志组对胃窦区、小肠组织c-kit、SCFmRNA和蛋白的表达无显著影响(P>0.05)。生远志组、蜜远志组及远志总皂苷组对大鼠胃起搏区组织c-kit、SCFmRNA和蛋白的表达均无显著影响(P>0.05)。④生远志组与远志总皂苷组能导致大鼠胃、小肠粘膜损伤面积显著增加(P<0.05,P<0.01)；而蜜远志对大鼠胃、小肠粘膜组织无明显损伤,而与生远志和皂苷组比较,有显著性差异(P<0.05)。⑤生远志组和总皂苷组可使大鼠胃、小肠粘膜细胞凋亡指数显著增加(P<0.01)；蜜远志对大鼠胃、小肠粘膜细胞凋亡指数无显著影响(P>0.05)。
结论：生远志10g／kg及其总皂苷5g／kg均能导致胃肠动力障碍、胃肠组织损伤,呈现胃肠靶器官毒性；而蜜炙远志10g／kg的胃肠动力障碍和胃肠组织损伤低于生远志,蜜炙确能降低远志的胃肠靶器官的毒副反应。其机理可能与以下因素相关：①调控c-kit/SCF信号通路,促进Cajal细胞功能恢复,改善胃肠电慢波,进而缓解胃肠动力障碍。②调控胃肠不同部位c-kit/SCF信号通路,促进胃肠协调运动的恢复。③缓解远志所造成的绒毛脱落,上皮细胞变性、细胞凋亡等胃肠粘膜损伤的病理学过程,改善胃肠粘膜的屏障功能。同时,蜜炙远志对胃肠运动障碍的缓解也在一定程度上改善胃肠粘膜的屏障功能。
综上,蜜炙远志通过调控胃肠Cajal间质细胞c-kit、SCFmRNA和蛋白的表达、促进胃肠协调运动的恢复、改善胃肠粘膜的屏障功能等多层次、多途径来实现其改善胃肠动力、减轻远志胃肠靶器官毒性的目的。远志中所含的总皂苷是其产生胃肠动力异常的主要物质基础。
Objective:Expound the biological mechanism of Radix Polygalae reducing the motility disorder in gastrointestinal tract by honey-fried,reveal the scientific connotation of traditional Chinese medicine reducing the stomach and intestines toxic by concoct in molecular level,It has great practical value and the academic significance of using Radix Polygalae reasonably and safely.
Methods:Application method of electrophysiology、molecular biology immunohistochemistry and so on. To explored the crude Radix P., its saponins and the honey-stir-baked Radix P. to the motility disorder in gastrointestinal tract,We did the following researches:①use BL-420 biologic analyzer to observe and record the electrophysiology in stomach and small intestine;②use immunohistochemistry to observe and record ICC in stomach and small intestine;③use RT-PCR and Western Blot to study the expression of c-kit mRNA and c-kit protein SCF mRNA and SCF protein in stomach and small intestine;④use HE to observe mucosa damage in stomach and small intestine;⑤use TUNEL to observe the Apoptosis in stomach and small intestine.
Result:①Crude Radix P. and its saponins can obviously inhibit slow wave in stomach and small intestine (P<0.01, P<0.05),but Honey-stir-baked Radix P. can not (P>0.05);②Crude Radix P. and its saponins can obviously decrease ICC (P< 0.01);Honey-stir-baked Radix P. can not;③Crude Radix P. and its saponins can remarkably decrease the expression of c-kit and SCF in Antral and small intestine (P <0.01);Honey-stir-baked Radix P. can not (P>0.05).while Radix P., its saponins and the honey-stir-baked Radix P.can not affect the expression of c-kit and SCF in Gastric pacing District (P>0.05);④Crude Radix P. and its saponins can obviously cause the mucosa damage in stomach and small intestine (P< 0.01),but Honey-stir-baked Radix P. can not (P>0.05);⑤Crude Radix P. and its saponins can obviously increase the Apoptosis in stomach and small intestine (P<0.01),but Honey-stir-baked Radix P. can not (P>0.05).
Conclusion:Crude Radix P.(10g/kg) and its saponins(5g/kg) can cause the motility disorder in gastrointestinal tract and damage the mucosa,but Honey-stir-baked Radix P. (10g/kg) can reduce this damage。The biological mechanism of Honey-stir-baked Radix P. ameliorate the motility and reduce the mucosal damage in gastrointestinal tract may related to the following factors:①Honey-stir-baked Radix P. can obviously adjust c-kit/SCF Signaling pathway, ameliorate SW in stomach and small intestine,which help relieve the motility disorder;②Honey-stir-baked Radix P. can obviously adjust c-kit/SCF Signaling pathway in differect part of Gastrointestinal tract,which can help coordinate the movement between stomach and small intestine;③Relieve the Pathological damage and Apoptosis in stomach and small intestin,which can protect the Mucosal barrier in gastrointestinal tract.
In brief, Honey-stir-baked Radix P. realize multi-level, the multi-ways to ameliorate Gastrointestinal motility and the mucosa's damage through adjust c-kit/SCF Signaling pathway,coordinate the movement between stomach and small intestine,relieve the Pathological damage and Apoptosis in stomach and small intestin.and protect the Mucosal barrier in gastrointestinal tract. Saponins is the main components of Crude Radix P. that causes the motility disorder in gastrointestinal tract.
方法：应用胃肠电生理学、分子生物学、免疫组织化学等方法和手段,探索蜜炙远志调控胃肠Cajal细胞及其关联机制。①采用BL-420生物机能实验系统,考察了对大鼠胃、肠电慢波的影响。②采用免疫组化方法,考察了对大鼠胃、小肠肌间神经丛c-kit阳性ICC细胞的影响。③采用RT-PCR法,考察了对大鼠胃和小肠c-kit、SCFmRNA表达水平的影响。④采用Western Blot法,考察了对大鼠胃和小肠c-kit、SCF蛋白表达水平的影响。⑤采用HE染色,观察了对大鼠胃和小肠组织形态的影响。⑥采用TUNEL法,观察了对大鼠胃和小肠组织细胞凋亡的影响。
结果：①生远志组能显著抑制胃电慢波振幅(P<0.05),其胃、小肠电慢波频率变异系数显著升高(P<0.01)。蜜远志组对胃和小肠电慢波频率、振幅无显著影响(P>0.05)；对胃和小肠电慢波频率变异系数、慢波振幅变异系数也无显著影响(P>0.05)。远志总皂苷组能显著抑制胃电振幅和小肠电慢波频率(P<0.01,P<0.05)；胃及小肠电慢波频率变异系数和慢波振幅变异系数显著增高(P<0.01)。②生远志组和总皂苷组能显著降低胃、小肠肌间神经丛c-kit阳性ICC细胞的含量(P<0.01)；而蜜远志组对胃、小肠肌间神经丛c-kit阳性ICC含量无显著影响(P>0.05)。③生远志组和远志总皂苷组能显著降低大鼠胃窦区、小肠组织中c-kit、SCFmRNA和蛋白的表达水平(P<0.01)；蜜远志组对胃窦区、小肠组织c-kit、SCFmRNA和蛋白的表达无显著影响(P>0.05)。生远志组、蜜远志组及远志总皂苷组对大鼠胃起搏区组织c-kit、SCFmRNA和蛋白的表达均无显著影响(P>0.05)。④生远志组与远志总皂苷组能导致大鼠胃、小肠粘膜损伤面积显著增加(P<0.05,P<0.01)；而蜜远志对大鼠胃、小肠粘膜组织无明显损伤,而与生远志和皂苷组比较,有显著性差异(P<0.05)。⑤生远志组和总皂苷组可使大鼠胃、小肠粘膜细胞凋亡指数显著增加(P<0.01)；蜜远志对大鼠胃、小肠粘膜细胞凋亡指数无显著影响(P>0.05)。
结论：生远志10g／kg及其总皂苷5g／kg均能导致胃肠动力障碍、胃肠组织损伤,呈现胃肠靶器官毒性；而蜜炙远志10g／kg的胃肠动力障碍和胃肠组织损伤低于生远志,蜜炙确能降低远志的胃肠靶器官的毒副反应。其机理可能与以下因素相关：①调控c-kit/SCF信号通路,促进Cajal细胞功能恢复,改善胃肠电慢波,进而缓解胃肠动力障碍。②调控胃肠不同部位c-kit/SCF信号通路,促进胃肠协调运动的恢复。③缓解远志所造成的绒毛脱落,上皮细胞变性、细胞凋亡等胃肠粘膜损伤的病理学过程,改善胃肠粘膜的屏障功能。同时,蜜炙远志对胃肠运动障碍的缓解也在一定程度上改善胃肠粘膜的屏障功能。
综上,蜜炙远志通过调控胃肠Cajal间质细胞c-kit、SCFmRNA和蛋白的表达、促进胃肠协调运动的恢复、改善胃肠粘膜的屏障功能等多层次、多途径来实现其改善胃肠动力、减轻远志胃肠靶器官毒性的目的。远志中所含的总皂苷是其产生胃肠动力异常的主要物质基础。
Objective:Expound the biological mechanism of Radix Polygalae reducing the motility disorder in gastrointestinal tract by honey-fried,reveal the scientific connotation of traditional Chinese medicine reducing the stomach and intestines toxic by concoct in molecular level,It has great practical value and the academic significance of using Radix Polygalae reasonably and safely.
Methods:Application method of electrophysiology、molecular biology immunohistochemistry and so on. To explored the crude Radix P., its saponins and the honey-stir-baked Radix P. to the motility disorder in gastrointestinal tract,We did the following researches:①use BL-420 biologic analyzer to observe and record the electrophysiology in stomach and small intestine;②use immunohistochemistry to observe and record ICC in stomach and small intestine;③use RT-PCR and Western Blot to study the expression of c-kit mRNA and c-kit protein SCF mRNA and SCF protein in stomach and small intestine;④use HE to observe mucosa damage in stomach and small intestine;⑤use TUNEL to observe the Apoptosis in stomach and small intestine.
Result:①Crude Radix P. and its saponins can obviously inhibit slow wave in stomach and small intestine (P<0.01, P<0.05),but Honey-stir-baked Radix P. can not (P>0.05);②Crude Radix P. and its saponins can obviously decrease ICC (P< 0.01);Honey-stir-baked Radix P. can not;③Crude Radix P. and its saponins can remarkably decrease the expression of c-kit and SCF in Antral and small intestine (P <0.01);Honey-stir-baked Radix P. can not (P>0.05).while Radix P., its saponins and the honey-stir-baked Radix P.can not affect the expression of c-kit and SCF in Gastric pacing District (P>0.05);④Crude Radix P. and its saponins can obviously cause the mucosa damage in stomach and small intestine (P< 0.01),but Honey-stir-baked Radix P. can not (P>0.05);⑤Crude Radix P. and its saponins can obviously increase the Apoptosis in stomach and small intestine (P<0.01),but Honey-stir-baked Radix P. can not (P>0.05).
Conclusion:Crude Radix P.(10g/kg) and its saponins(5g/kg) can cause the motility disorder in gastrointestinal tract and damage the mucosa,but Honey-stir-baked Radix P. (10g/kg) can reduce this damage。The biological mechanism of Honey-stir-baked Radix P. ameliorate the motility and reduce the mucosal damage in gastrointestinal tract may related to the following factors:①Honey-stir-baked Radix P. can obviously adjust c-kit/SCF Signaling pathway, ameliorate SW in stomach and small intestine,which help relieve the motility disorder;②Honey-stir-baked Radix P. can obviously adjust c-kit/SCF Signaling pathway in differect part of Gastrointestinal tract,which can help coordinate the movement between stomach and small intestine;③Relieve the Pathological damage and Apoptosis in stomach and small intestin,which can protect the Mucosal barrier in gastrointestinal tract.
In brief, Honey-stir-baked Radix P. realize multi-level, the multi-ways to ameliorate Gastrointestinal motility and the mucosa's damage through adjust c-kit/SCF Signaling pathway,coordinate the movement between stomach and small intestine,relieve the Pathological damage and Apoptosis in stomach and small intestin.and protect the Mucosal barrier in gastrointestinal tract. Saponins is the main components of Crude Radix P. that causes the motility disorder in gastrointestinal tract.
引文
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