Objective：To explore the significance of colonic epithelial cell apoptosis and tumor necrosis factorα（TNF-α）changing in pathogenesis of melanosis coli（MC）in guinea pig and the molecular mechanism of rhubarb（Rh...Objective：To explore the significance of colonic epithelial cell apoptosis and tumor necrosis factorα（TNF-α）changing in pathogenesis of melanosis coli（MC）in guinea pig and the molecular mechanism of rhubarb（Rhu）in inducing the disease,by means of using different dosages of Rhu to induce the disease. Methods：One hundred and forty-four male guinea pigs,clean grade,were randomized according to their body weight into 5 groups,the untreated normal group and the 4 Rhu groups treated,respectively,with different doses of Rhu,3 g/kg·d for low dose（Rhu-I）group,6 g/kg·d for moderate dose（Rhu-m）group,12 g/kg·d for high dose（Rhu-h）group and 24 g/kg·d for super-high dose（Rhu-s）group via gastric infusion.All animals were sacrificed 60 days later,their viscera were taken for observing the pathologic and morphologic changes with HE, melanin and melatonin staining,and the apoptosis of colonic epithelial cells was detected with TUNEL stain and transmission electric microscopy.In addition,the levels of TNF-αin serum and colonic tissue were measured using ELISA and RT-PCR.Results：The pathological changes of MC could be found by naked eye in all Rhu groups,especially apparent at caecum and proximal end of colon,but did not found in gallbladder,jejunum and ileum.In normal guinea pigs,the colonic membrane was pink in color with no apparent pigment deposition. Membranous color deepened in the Rhu groups depending on the dosage of Rhu used.MC scoring showed the highest scores revealed in the Rhu-s group（6.00±0.00）,which was significantly different to those in the Rhu-I （3.86±0.69）,Rhu-m（4.43±0.79）and Rhu-h groups（4.88±0.35,all P0.05）.Levels of cell apoptosis in colon and TNF-αin serum in all Rhu groups were higher than those in the normal group（P0.01）,but showed no significant difference among the Rhu groups（P0.05）.Moreover,a positive correlation was found in the degree of induced MC with apoptosis rate and TNF-αlevel.Conclusions：Rhu（anthraquinone purgatives）had 展开更多
基金Supported by Zhejiang Provincial Funds of Natural Sciences (No.X206959)the Key Project Item of Hangzhou Municipal Administration of Science and Technology(No.2006533Q15)
文摘Objective：To explore the significance of colonic epithelial cell apoptosis and tumor necrosis factorα（TNF-α）changing in pathogenesis of melanosis coli（MC）in guinea pig and the molecular mechanism of rhubarb（Rhu）in inducing the disease,by means of using different dosages of Rhu to induce the disease. Methods：One hundred and forty-four male guinea pigs,clean grade,were randomized according to their body weight into 5 groups,the untreated normal group and the 4 Rhu groups treated,respectively,with different doses of Rhu,3 g/kg·d for low dose（Rhu-I）group,6 g/kg·d for moderate dose（Rhu-m）group,12 g/kg·d for high dose（Rhu-h）group and 24 g/kg·d for super-high dose（Rhu-s）group via gastric infusion.All animals were sacrificed 60 days later,their viscera were taken for observing the pathologic and morphologic changes with HE, melanin and melatonin staining,and the apoptosis of colonic epithelial cells was detected with TUNEL stain and transmission electric microscopy.In addition,the levels of TNF-αin serum and colonic tissue were measured using ELISA and RT-PCR.Results：The pathological changes of MC could be found by naked eye in all Rhu groups,especially apparent at caecum and proximal end of colon,but did not found in gallbladder,jejunum and ileum.In normal guinea pigs,the colonic membrane was pink in color with no apparent pigment deposition. Membranous color deepened in the Rhu groups depending on the dosage of Rhu used.MC scoring showed the highest scores revealed in the Rhu-s group（6.00±0.00）,which was significantly different to those in the Rhu-I （3.86±0.69）,Rhu-m（4.43±0.79）and Rhu-h groups（4.88±0.35,all P0.05）.Levels of cell apoptosis in colon and TNF-αin serum in all Rhu groups were higher than those in the normal group（P0.01）,but showed no significant difference among the Rhu groups（P0.05）.Moreover,a positive correlation was found in the degree of induced MC with apoptosis rate and TNF-αlevel.Conclusions：Rhu（anthraquinone purgatives）had
