| BackgroundFunctional diarrhea is a syndrome characterized by persistent recurrence of dilute(pasty)or watery feces without abdominal pain or discomfort.Roman IV diagnostic criteria are more than 25%of the stools are diluted or water-like,without obvious abdominal pain or abdominal distension discomfort.Symptoms occur at least 6 months before diagnosis,and meet the above diagnostic criteria in the past 3 months.The pathogenesis of functional diarrhea is not clear.Many factors may be the cause of its disease,for example:gastrointestinal motility abnormalities,visceral hypersensitivity,gastrointestinal electrophysiological disorders,intestinal microecology disorders,gastrointestinal hormone secretion abnormalities,genetic and environmental factors,psychological factors,etc.Most of the studies do not distinguish functional diarrhea from IBS strictly.Compared with the pathogenesis of IBS,there are relatively few studies on the mechanism of functional diarrhea,which need to be further explored by researchers.Western medicine treatment mostly relies on symptomatic treatment.Diarrhea can be divided into acute diarrhea and chronic diarrhea according to the length of the course of disease.The environment of diarrhea can be the basis for clinicians to judge the cause of diarrhea.According to the pathogenesis,diarrhea can be divided into secretory diarrhea,permeable diarrhea,exudative diarrhea and gastrointestinal dynamic diarrhea.The essence of diarrhea is that the normal physiological balance of water and electrolyte secretion and absorption in the intestinal tract is broken.Therefore,a thorough understanding of the process of water and electrolyte absorption and secretion in the gastrointestinal tract is the premise and basis for studying the pathogenesis of diarrhea.Functional diarrhea belongs to the category of "Xiexie" according to its clinical manifestations.Functional diarrhea is mainly caused by exogenous pathogens,stomach,dietary fatigue,emotional disorders,weakness of vegetative body and so on,which lead to deficiency of spleen and stomach qi,dysfunction of spleen and stomach,intestinal clear secretion,conduction dysfunction."Su Question·Zang Qi Fa Shi Lun”:”Spleen disease patients……Spleen deficiency is accompanied by gastrointestinal ringing,diarrhea and indigestion of diet.If other viscera and spleen,such as liver-muke spleen,liver-qi discomfort,transverse violation of the spleen,resulting in spleen and stomach weakness,spleen dysfunction,there is "stagnation of liver-qi".Two ribs pain and diarrhea,known as liver catharsis.Or Kidney Yang deficiency,life door fire decline,fire not warm soil,spleen warming."Zhang Shiyitong" Volume 7:"Five more diarrhea,kidney deficiency and loss of its closed duty.Damp pathogen is the main pathological factor causing functional diarrhea,dampness is Yin pathogen,and it is easy to restrain spleen-yang.There is a saying in "No dampness but no diarrhea" in Medical Zong Bishu.The spleen is Yang soil,like dryness and disgust dampness.Therefore,the spleen and stomach are weak,and water vapor overflows,depression and prolonged heat dissipate.At the same time,it can cause external dampness and heat offenders,leading to dampness and heat accumulate Therefore,the main pathogenesis of functional diarrhea is weakness of spleen and stomach,or evolved on the basis of weakness of spleen and stomach.In this study,we used the rat model of functional diarrhea with spleen deficiency syndrome to study the effect of short-circuit current technology on ion transport in distal colon mucosa and elucidate its transport mechanism.We hope that this basic research can provide a theoretical basis for the pathogenesis and clinical treatment of functional diarrhea.Purpose1.To explore the possible effect of Jianpi prescription on distal colonic mucosal epithelium in rats,different doses of Jianpi prescription were given to FDr rats with spleen deficiency syndrome in vitro.2.To observe the ionic transport electric activity of Jianpi prescription in vitro,and to elucidate the mechanism of Shenling Baizhu powder and its main spleen-strengthening drugs regulating ion channels in colonic epithelial cells of rats.ReseacherExperiment 1,Establishment and evaluation of rat model of spleen deficiency syndrome combined with syndrome of FDrObjective:To establishment and evaluation of rat model of spleen deficiency syndrome combined with syndrome of FDrMaterials and Methods:Twenty,SPF-grade 3-week-old Wistar rats,(50±5)g.Rats were randomly divided into normal group and model group with 10 rats in each group.The normal group was fed normally,while the model group was fed with high lactose forage for 14 days.At the same time,rats were placed on a small platform in a special square tank from 18:00 a day to 8:00 the next day for 14 consecutive days.During the modeling period,the general condition,body weight,food intake,drinking water,grip,fecal water content,serum D-xylose,amylase and lactic acid content were observed.Results1.General Situation:Rats in the normal group had normal mental state,reflecting agility,hyperactivity,bright hair,normal stool formation,yellowish-brown color,reduced activity,depression,eyes squinting,sleepiness,loss of appetite,weight loss,emaciation,hair irregularity,darkening color,loose stool,and even water-like stool.2.Compared with the normal group,the weight,food intake and water intake of the model group were significantly lower(P<0.05).3.Grasp measurement:Compared with the normal group,the grip force of the model group was significantly lower(P<0.05).4.Fecal water content:Compared with the normal group,the fecal water content of the model group was significantly higher than that of the normal group(P<0.05).5.Serological indicators:Compared with the normal group,the serum D-xylose and amylase content in the model group decreased,while the lactate content increased,the difference was statistically significant(P<0.05).Experiment 2,Effect of Shenling Baizhu Powder and Its Main Spleen-invigorating Drugs on Epithelial Ion Transport in Rats with Spleen Deficiency Syndrome of FDrObjective:To observe the effects of Shenling Baizhu Powder and different doses of main drugs on distal colonic mucosal epithelium in ratsMaterials and Methods:Rats were randomly divided into normal group and model group.Rat models of functional diarrhea with spleen deficiency syndrome were established by feeding high lactose diet and adding small platforms.After successful modeling,distal colonic mucosa of normal group and model group was taken and placed on short circuit current equipment.The difference of basic physiological current between model group and normal group was compared.In vitro,different concentrations of Baizhu,Fuling,Dangshen and Shenling Baizhu powder were given to observe the effects of drugs on short-circuit current in normal and model rats.Results1.In vitro,the basal physiological current of the model rats was slightly lower than that of the normal group,but there was no significant difference(P<0.05).2.The short-circuit current values of normal and model rats decreased with the increasing concentration of Baizhu,showing a bidirectional effect,and the difference was statistically significant(P<0.05).3.The short-circuit current values of normal rats and model rats increased with the increasing concentration of Fuling,Dangshen and Shenling Baizhu powder,showing a two-way effect,the difference was statistically significant(P<0.05).Experiment 3,Effects of Shenling Baizhu Powder and its main spleen-strengthening drugs on epithelial ion transport in rats with spleen deficiency syndrome induced by FDrObjective:To explore the mechanism of ion transport in colonic mucosa epithelium by different prescriptions for invigorating the spleen in vitro.Materials and Methods:The rats were randomly divided into normal group and model group.The rats model of functional diarrhea with spleen deficiency syndrome was established by feeding high lactose diet and superimposing small platform method.After successful modeling,the distal colonic mucosa of rats in the normal group and the model group was placed on short-circuit current equipment,and different ion channel blockers and ion replacement solutions were given to intervene.Then add Baizhu,Fuling,Dangshen and Shenling Baizhu powder to observe the changes of short-circuit current caused by drugs in normal rats and model rats.Then,by analyzing the changes of current,we can clarify the mechanism of ion transport of drugs to mucosa.Results1.TTX and indomethecin were added to the basement membrane of mucosal epithelium to observe the effect of Jianpi Recipe on Isc of colonic mucosal epithelial cells in normal and model rats.Among them,Isc caused by Baizhu,Dangshen and Shenling Baizhu powder decreased significantly(P<0.05);Isc caused by Fuling decreased,with no significant difference compared with the basic current(P>0.05).2.When Baizhu was added into Krebs solution without Cl-,Cl-/HCO3-,the changes of short-circuit current caused by normal rats and model rats were observed to decrease,with significant difference(P<0.05);in Krebs solution without HCO3-,the changes of short-circuit current were not significant(P>0.05).3.When Dangshen was added into Krebs solution without CI-,HCO3-,and Cl-/HCO3-,the short circuit current changes induced by normal rats and model rats were observed to decrease,with significant difference(P<0.05).4.When Shenling Baizhu powder was added into Krebs solution without Cl-,HCO 3-,and Cl-/HCO3-,the changes of short-circuit current induced by normal rats and model rats were observed to be reduced,and the difference was statistically significant(P<0.05).5.When DPC was added to the parietal membrane side and bumetanide and TEA were added to the basement membrane side,the ISC caused by Baizhu decreased significantly(P<0.05),and amiloride,a blocker of Na+ channel,was added to the parietal membrane side.After DIDS on the basement membrane side,the change of current caused by Baizhu macrocephala was not affected,with no significant difference(P>0.05).6.When DPC and amloride were added to the parietal membrane side and bumetanide,TEA and DIDS were added to the basement membrane side,Isc caused by Dangshen decreased significantly(P<0.05).7.When DPC and amiloride were added to the parietal membrane side and bumetanide,TEA and DIDS were added to the basement membrane side,Isc caused by Shenling Baizhu powder decreased significantly(P<0.05).Conclusions1.The animal model of functional diarrhea can be successfully established by feeding high lactose diet plus modified small platform method,which has the characteristics of spleen deficiency syndrome.2.In vitro,Shenling Baizhu Powder and its main spleen-invigorating drugs can directly act on colonic mucosa.The spleen-invigorating prescriptions and spleen-invigorating drugs can exert their bidirectional regulatory effects on ion transport from different angles,and show a dose-dependent manner.3.Baizhu may affect the absorption of Cl-by regulating Cl-channels on the parietal membrane and K-Cl transporters on the basement membrane,and the secretion of K+by regulating K channels on the parietal membrane.4.Dangshen may affect the absorption of Na+,K+,Cl-channel and NKCC/KCC transporter on the parietal membrane,as well as the secretion of HCO3-on the parietal side by regulating Na+,K channel on the parietal membrane.5.Shenling Baizhu powder may affect the absorption of Na+,K+,Cl-channel and NKCC/KCC transporter on the parietal membrane,as well as the secretion of HCO3-on the parietal side by regulating Na+,K+channel on the parietal membrane. |
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