Curative Effect and Mechanism of Traditional Chinese Medicine in Treatment of Diabetic Gastroenteropathy： A Review / 中国实验方剂学杂志

Diabetic gastroenteropathy is a serious chronic complication that accompanies the progression of diabetes mellitus， severely impacting patients' quality of life and overall health. Nearly half of diabetic patients experience symptoms such as nausea， vomiting， early satiety， abdominal distension， and abdominal pain， which increases their anxiety and depression， prompting frequent medical visits and further burdening the healthcare system. In-depth research into the pathogenesis of diabetic gastroenteropathy has identified several core mechanisms， including hyperglycemia， autonomic and enteric nervous system dysfunction， abnormal secretion of gastrointestinal hormones， macrophage polarization， brain-gut axis dysregulation， microRNA deficiency， and oxidative stress-induced damage and apoptosis of interstitial cells of Cajal （ICC）. Current clinical treatments mainly rely on prokinetic and antiemetic drugs. However， their notable adverse effects and diminishing efficacy with long-term use remain pressing issues. Traditional Chinese medicine （TCM）， with its unique theoretical framework and extensive practical experience， potent in prescription formulation and acupoint selection guided by holistic concepts and syndrome differentiation， has gradually become an important option for treating diabetic gastroenteropathy. Numerous studies have confirmed that mechanisms include improving gastrointestinal hormone secretion， repairing ICC damage， regulating the nervous system， reducing oxidative stress， and modulating the brain-gut axis. These findings provide new insights into the treatment of diabetic gastroenteropathy. This article summarized the pathogenesis of diabetic gastroenteropathy and reviewed recent research on Chinese medicine and acupuncture-moxibustion therapy in improving gastrointestinal motility for diabetic gastroenteropathy treatment， aiming to offer clinical treatment insights and highlight the need for further research to explore comprehensive and individualized treatment approaches， providing better strategies for managing diabetic gastroenteropathy.

Banxia Xiexintang Regulates Autophagy of Interstitial Cells of Cajal in Gastric Antrum of Rats with Gastric Electric Dysrhythmia / 中国实验方剂学杂志

ObjectiveTo observe the effect of Banxia Xiexintang on the autophagy of interstitial cells of Cajal （ICCs） in the gastric antrum of rats with gastric electric dysrhythmia， and explore the protective effect and regulatory mechanism. MethodThirty-two SD rats were randomly assigned into a normal group， a model group， a Banxia Xiexintang （24.68 g·kg-1） group， and a positive drug （2.7 mg·kg-1） group. The rat model of gastric electric dysrhythmia was established by the method of dieting every other day and drinking dilute hydrochloric acid， and Banxia Xiexintang and the positive drug were administrated for intervention. The body weight of each rat was recorded weekly. The gastric electric activity was recorded by the biological function experimental system. The ultrastructural changes of the gastric antrum tissue were observed by a transmission electron microscope. The co-expression of receptor tyrosine kinase （c-kit）/mammalian homolog of yeast Atg6 （Beclin1） in the gastric antrum tissue was detected by double immunofluorescence labeling method. The expression of microtubule-associated protein 1 light chain 3B （LC3B） and p62 protein in the gastric antrum tissue was determined by Western blot， and the LC3BⅡ/Ⅰ ratio was calculated. ResultCompared with the normal group， the modeling reduced the body weight （P<0.01） and decreased the dominant frequency and dominant power of gastric electricity （P<0.01）. In addition， the modeling caused ultrastructural damage of ICCs in gastric antrum， degeneration and necrosis of organelles， and appearance of a small number of autophagic vesicles. The results of double immunofluorescence labeling showed that the modeling inhibited the positive expression of c-kit and promoted the positive expression of Beclin1 in gastric antrum tissue. Western blot results showed that the modeling increased the ratio of LC3BⅡ/Ⅰ （P<0.01） and down-regulated the expression of p62 protein （P<0.01） in the gastric antrum tissue. Compared with the model group， Banxia Xiexintang and the positive drug increased the body weight （P<0.01） and the dominant frequency and dominant power of gastric electricity （P<0.01）， repaired the ultrastructural damage of ICCs in gastric antrum tissue， promoted the positive expression of c-kit and inhibited the positive expression of Beclin1 in the gastric antrum tissue. Furthermore， Banxia Xiexintang up-regulated the expression of p62 （P<0.05） and inhibited the transformation of LC3BⅠ into LC3BⅡ in gastric antrum tissue （P<0.05）. ConclusionBy regulating the expression of autophagy-related proteins， Banxia Xiexintang can reduce the autophagy and regulate the number and structure of ICCs and thus improve the gastric electric rhythm of rats， which preliminarily explains the mechanism of Banxia Xiexintang in the treatment of epigastric stuffiness.

Effect of Dahuang Lingxian prescription on the scf/c-kit signaling pathway in gallbladder interstitial cells of Cajal in a guinea pig model of cholesterol gallstone / 临床肝胆病杂志

Objective To investigate the expression levels of scf and c-kit under the regulation of Dahuang Lingxian prescription and the possible mechanism of its effect on gallbladder dynamics, and to provide a theoretical basis for Dahuang Lingxian prescription in preventing the development and recurrence of cholesterol gallstone. Methods A total of 45 specific pathogen-free healthy male guinea pigs were randomly divided into normal group, model group, and traditional Chinese medicine (TCM) group. The guinea pigs in the normal group were fed with normal diet, and those in the model group and the TCM group were fed with high-fat lithogenic diet. After 8 weeks of feeding, 5 guinea pigs were randomly selected from each group, and successful modeling was determined if gallstone was observed with the naked eye in more than 4 guinea pigs. After successful modeling, the guinea pigs in the TCM group were given Dahuang Lingxian prescription by gavage, and those in the model group were given an equal volume of normal saline by gavage. After 8 consecutive weeks of administration by gavage, gallbladder tissue samples were collected, and HE staining was used to observe the pathological changes of gallbladder tissue; Western blot was used to measure the expression level of tumor necrosis factor-α (TNF-α) in gallbladder tissue; immunohistochemistry was used to measure the protein expression levels of scf and c-kit in gallbladder smooth muscle tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference multiple comparison method was used for further comparison between two groups. Results HE staining showed marked inflammation of gallbladder tissue in the model group, and compared with the model group, the TCM group had a significantly lower degree of inflammation. Western blot showed that the model group had the highest expression level of TNF-α in gallbladder tissue, followed by the TCM group and the normal group ( P < 0.05); immunohistochemistry showed that compared with the model group, the normal group and the TCM group had significantly higher protein expression levels of scf and c-kit in gallbladder smooth muscle tissue ( P < 0.05). Conclusion Dahuang Lingxian prescription can enhance the dynamic function of the gallbladder, possibly by upregulating the scf/c-kit signaling pathway in interstitial cells of Cajal in gallbladder.

Exploring the Theoretical Basis of Qi-Shi-Sheng-Jiang-Gui-Yuan Decoction in Treating GERD Based on the Correlation Between"Regulating Pivot with Pivot"and ICC Mitophagy / 世界科学技术-中医药现代化

The Gastroesophageal reflux disease(GERD)is related to the dynamic disorder of the digestive tract caused by the imbalance of the viscera and meridians.The spleen and stomach are the hub of the qi machinery,transforming the essence of water and valley into energy and regulating the Yin and Yang of all bodies.The sympathetic balance between Ren-Du and Qi is the motivity of the spleen and stomach.Interstitial cells of Cajal(ICC)are the hub of digestive motility,which can maintain mitochondrial energy metabolism through mitochondrial autophagy and improve the digestive motility.Therefore,in this paper,the molecular biological basis of GERD was discussed based on the"regulating pivot with pivot"theory that the pivots of viscera and meridians drive ICC mitochondrial energy balance.It also explains the feasibility of Qi-Shi-Sheng-Jiang-Gui-Yuan Decoction in treating GERD based on"regulating pivot with pivot",which is helpful to realize the microscopization and concretization of"regulating pivot with pivot"theory and realize the modernization of TCM theory.

Luteolin ameliorates loperamide-induced functional constipation in mice

Functional constipation (FC) is one of the most common gastrointestinal disorders characterized by hard stools and infrequent bowel movements, which is associated with dysfunction of the enteric nervous system and intestinal motility. Luteolin, a naturally occurring flavone, was reported to possess potential pharmacological activities on intestinal inflammation and nerve injury. This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoactive intestinal polypeptide (VIP), and acetylcholine (ACh), as well as interstitial cells of Cajal (ICC) biomarker KIT proto-oncogene, receptor tyrosine kinase (C-Kit), and anoctamin-1 (ANO1), implying that luteolin mediated enhancement of colonic function and contributed to the anti-intestinal dysmotility against loperamide-induced FC. Additionally, luteolin decreased the upregulation of aquaporin (AQP)-3, AQP-4, and AQP-8 in the colon of FC mice. In summary, our data showed that luteolin might be an attractive option for developing FC-relieving medications.

Gist sincrónico con adenomioma gástrico: Reporte de caso y revisión de la literatura / Synchronous gist with gastric adenomyoma: Case report and literature review

Introducción: La colisión de dos tumores de diferente estirpe celular en un mismo órgano es infrecuente; a pesar de las asociaciones descritas en la literatura, el hallazgo de GIST con adenomioma en sincronismo, llama aún más la atención debido a sus distintos orígenes celulares. Reporte de caso: Presentamos el caso de una paciente mujer de 57 años de edad, quien es sometida a cirugía de resección doble en cuña, y distintos exámenes incluido el anátomo-patológico. Conclusión: Se demuestra la presencia de tumores sincrónicos, GIST gástrico y adenomioma gástrico, a pesar de la infrecuencia de este hallazgo.

Background:The collision of two tumors of different cell lines in the same organ is infrequent; even though, the associations described in the literature, the finding of synchronous GISTwith adenomyoma draws even more attention due to its different cellular origins. We present the case of a 57-year-Case report:old female patient who underwent double wedge resection surgery and various examinations, including pathology. Conclusion:The presence of synchronous tumors, gastric GIST and gastric adenomyoma is demonstrated,despite the infrequency of this finding.

Expression and significance of HERG protein in Cajal interstitial cells of gallbladder tissue in patients with gallbladder stones / 中华肝胆外科杂志

Objective:To investigate the expression and significance of human ether-a-go-go related gene (HERG) protein in interstitial cells of Cajal (ICC) in patients with gallbladder stones.Methods:The gallbladder tissues of 60 patients with gallbladder diseases who underwent cholecystectomy from January 2018 to December 2020 in the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital were collected, including 36 males and 24 females, aged (46.0±14.0) years. They were divided into two groups according to whether there were gallstones: gallstone group and control group (patients with gallbladder polyps and gallbladder adenomyosis), with 30 cases in each group. Color ultrasound was used to detect and calculate the gallbladder contraction rate. The neck, body and bottom tissues of the gallbladder were excised and sectioned. The expression of HERG protein and CD117 ( marker of ICC) was detected by immunofluorescence staining, immunohistochemistry and Western blot.Results:The gallbladder contraction rate in the gallstone group was (65.8±4.1)%, lower than that in the control group (73.8±5.3)%, with a statistically significant difference ( t=4.14, P<0.001). Immunohistochemistry showed that HERG protein was mainly distributed in the mucosal layer of gallbladder tissue, which was pale brown. The relative expression of HERG protein at the bottom of gallbladder in the gallstone group was (0.293±0.102), lower than that in the control group (0.694±0.059), with a statistically significant difference ( t=3.38, P=0.027). Immunofluorescence staining showed that HERG protein was mainly distributed in ICC of gallbladder epithelium. HERG protein expression in ICC at the bottom of gallbladder in gallstone group was lower than that in control group, while HERG protein expression at the neck and body of gallbladder had no significant difference. Conclusion:There are ICC and HERG protein in gallbladder tissue of patients with gallstone. The decrease of gallbladder contraction rate may be related to the decrease of HERG protein expression in ICC in gallbladder bottom tissue.

Protective Effect of Tangshen Formula () on Interstitial Cells of Cajal in Colon of Diabetic Rats / 中国结合医学杂志

OBJECTIVE@#To explore the effect of Tangshen Formula (, TSF), a Chinese herbal medicine, on interstitial cells of Cajal (ICC) in the colon of diabetic rats.@*METHODS@#Fifty-four male Wistar rats were randomly divided into normal control (NC, n=14) and high-fat diet (HFD) groups (n=40). After 6 weeks, the rats in the HFD group were injected intraperitoneally streptozotocin once (30 mg/kg). Thirty rats with fasting blood glucose higher than 11.7 mmol/L were randomly divided into diabetes (DM) and TSF groups, 15 rats in each group. Rats in the NC and DM groups were intragastrically administered with saline, and those in the TSF group were given with TSF (2.4 g/kg) once daily for 20 weeks. Expression levels of Bax, Bcl-2, and caspase-3 in colonic smooth muscle layer were measured by Western blotting and immunohistochemical staining. The number of ICC was determined by immunohistochemical staining. Immunofluorescence was used for analyzing the ratio of classically activated macrophages (M1) and alternatively activated macrophages (M2) to total macrophages. Electron microscopy was used to observe the epithelial ultrastructure and junctions.@*RESULTS@#TSF appeared to partially prevented loss of ICC in DM rats (P<0.05). Compared with the NC group, expression levels of Bcl-2, Bax, caspase-3, and TNF-α as well as the ratio of M1 to total macrophages increased in DM rats (all P<0.05), and the ratio of M2 to total macrophages decreased (P<0.05 or P<0.01). Compared with the DM group, TSF decreased the expression levels of abovementioned proteins and restore M2 to total macrophages ratio (P<0.05 or P<0.01). TSF appeared to attenuate the ultrastructural changes of epithelia and improve the tight and desmosome junctions between epithelia reduced in the DM rats.@*CONCLUSION@#Reduced number of ICC in DM rats may be associated with damage of the intestinal barrier. The protective effects of TSF on ICC may be through repair of the epithelial junctions, which attenuates inflammation and inflammation-initiated apoptosis in colon of DM rats.

Study of the effect of inhibition of c-Kit and Cx43 on bladder contractile function and its mechanism of action / 安徽医科大学学报

Objective @#To investigation of the interaction between interstitial cells of Cajal (ICCs) and connexin 43 ( Cx43) in bladder contraction and its significance．@*Methods @#Eighty male guinea pigs were randomly divided into blank control group，Glivec group，Gap27 group and Glivec + Gap27 group．Four groups of guinea pigs were per- fused with saline，Glivec，Gap 27，and Glivec + Gap 27 every morning for 2 months．Success of urodynamic testing model after 2 months．Bladder tissue was collected for an in vitro muscle strip test to detect muscle contraction in each group．Correlation between c-Kit and Cx43 was detected by immunofluorescence．The interaction between c- Kit and Cx43 in the bladder was further validated by qRT-PCR and Western blot．Ultrastructural changes in the muscle layer of the bladder were observed by electron microscopy. @*Results @#Urodynamics revealed increased blad- der compliance in the experimental group compared to the blank control group (P＜0. 05) ; bladder compliance increased in the Glivec + Gap27 group compared to the Glivec and Gap27 groups (P＜0. 01) ．In vitro muscle strip experiments revealed that the frequency and tone of bladder muscle strip contractions were lower in the experimental group compared to the blank control group (P＜0. 05) ，and that muscle strip contractions were weaker in the ex- perimental group after administration of acetylcholine (ACH) compared to the control group(P＜0. 05) ．Immuno- fluorescence showed that c-Kit was co-expressed with Cx43 on ICCs cells．qRT-PCR and Western blot suggested that the protein expression level and gene expression level of Cx43 in bladder tissues were lower after inhibition of c-Kit than in the blank control (P＜0. 05) ; after inhibition of Cx43，the protein expression level and gene expres- sion level of c-Kit in bladder tissues the levels of c-Kit protein expression and gene expression in bladder tissues were lower than those in the blank control group (P＜0. 05) ．Electron microscopy revealed that the mitochondrial structure of bladder smooth muscle was disrupted after simultaneous inhibition of c-Kit and Cx43．@*Conclusion@#Cx43 is expressed on bladder ICCs and the two may be jointly involved in regulating bladder contractile function ; the joint reduction of Cx43 and c-Kit may have disrupted the mitochondria of bladder smooth muscle，affecting its function and consequently bladder contractile function.

Role of Gastrointestinal Muscularis Macrophages in Regulation of Gastrointestinal Motility / 胃肠病学

Recent studies have found a special class of macrophages, muscularis macrophages (MMs), in the gastrointestinal tract, which interacts with enteric neuron (EN), interstitial cells of Cajal (ICC), and smooth muscle cells (SMC) to maintain normal intestinal motility. MMs can undergo phenotypic and other changes under altered intestinal microbiota, inflammation, or stress, and act on EN, ICC, or SMC through multiple mechanisms, ultimately affecting gastrointestinal motility. This article reviewed the mechanism of gastrointestinal MMs regulating gastrointestinal motility and role in gastrointestinal motility disorder diseases.

Regulative effect of Rhubarb dispensing granule on autophagy and gastrointestinal motility of Cajal interstitial cells in rats with chronic transit constipation / 国际中医中药杂志

Objective:To study the regulative effect of Rhubarb dispensing granule on autophagy and gastrointestinal motility of Cajal interstitial cells in rats with chronic transit constipation (STC).Methods:A total of 75 rats were randomly divided into control group, model group, low, medium and high dose groups with 15 rats in each group. Except for the control group, the STC rat models were established by intragastric administration of compound diphenoxylate suspension. Rats in low, medium and high dose groups were given Rhubarb dispensing granule of 1, 2 and 4 g/kg by gavage respectively, while rats in control group and model group were given normal saline with the same volume by gavage, once a day for 14 consecutive days. Fecal moisture content and intestinal propulsion rate were measured. The serum levels of substance P (SP), vasoactive intestinal peptide (VIP), NO and NOS were detected by ELISA. The pathological changes of colon tissue were observed by HE staining. The c-kit level in colon tissue was detected by immunohistochemistry. The mRNA and protein levels of c-kit and Beclin1 in colon tissue were detected by PCR and Western blot.Results:Compared with the model group, the fecal moisture content, the carbon pushing distance and the intestinal pushing rate of the low, medium and high dose groups were significantly increased ( P<0.05), the serum SP level was increased ( P<0.05), the serum VIP, NO and NOS levels of the low, medium and high dose groups were decreased ( P<0.05), and the average expression score of c-kit in colon tissue of the low, medium and high dose groups was significantly increased ( P<0.05). The levels of c-kit mRNA (2.33 ± 0.35, 3.04 ± 0.17, 3.83 ± 0.23 vs. 0.61 ± 0.07) and protein (0.42 ± 0.06, 0.60 ± 0.07, 0.79 ± 0.08 vs. 0.22 ± 0.04)in colon tissue of rats in low, medium and high dose groups were increased ( P<0.05), and Beclin1 mRNA (4.17 ± 0.37, 3.35 ± 0.44, 1.05 ± 0.28 vs. 6.04 ± 0.31) and protein (0.76 ± 0.11, 0.57 ± 0.08, 0.43 ± 0.05 vs. 0.91 ± 0.06) were decreased ( P<0.05). Conclusion:Rhubarb dispensing granule could significantly increase the fecal moisture, intestinal motility rate, serum SP level and colonic tissue c-kit level, decrease serum VIP, NO, NOS level and colonic tissue Beclin1 level in rats with chronic transit constipation, and then inhibit autophagy of Cajal interstitial cells and regulate gastrointestinal motility in rats with chronic transit constipation.

Study on the mechanism of Dahuangfuzi decoction in improving intestinal motility disorder of rats with severe acute pancreatitis / 中华急诊医学杂志

Objective:To explore the mechanism of Dahuangfuzi decoction on intestinal motility disorder by observing its effect on serum motilin, Cajal interstitial cells and motilin receptor in rats with severe acute pancreatitis (SAP).Methods:Eighteen clean male Sprague-Dawley rats were randomly divided into the control group, SAP group and Dahuangfuzi group ( n=6 each group). The SAP rat model was prepared by retrogradely injected 4% sodium taurocholate into cholangiopancreatic duct. The rats in the SAP group were given 2 mL normal saline (37℃) enema at 12 and 24 h after operation. The rats in the Dahuangfuzi group was given 2 mL Dahuangfuzi decoction (37℃) enema at 12 and 24 h respectively. For the control group, the pancreas was exposed in the same way and then the abdomen was closed. Forty-eight h after operation, the abdominal aorta blood samples were taken for determination of serum endotoxin and amylase, and for detection of serum motilin by enzyme-linked immunosorbent assay (ELISA); the pathological changes of pancreas and ileum were observed by hematoxylin-eosin (HE) staining. The expression of c-kit and motilin receptor protein in ICC in ileum tissue was detected by immunohistochemistry. Results:Compared with the control group, the levels of serum endotoxin and amylase in the SAP group were significantly higher [(504.98±88.81) pg/mL vs. (17.76±5.01) pg/mL; (532.28±66.53) vs. (69.45±3.61) U/L, P<0.05], while the levels of serum motilin were significantly lower [(195.4±6.7) ng/L vs. (301±8.10) ng/L, P<0.05], and the scores of c-kit and motilin receptor protein were decreased ( P<0.05); compared with the SAP group, the levels of serum endotoxin and amylase in the Dahuangfuzi group were significantly reduced [(189.9±38.23) pg/mL vs. (504.98±88.81) pg/mL; (294.23±25.66) vs. (532.28±66.53) U/L, P<0.05], while the levels of serum motilin were significantly increased [(264.2±8.3) ng/L vs. (195.4±6.7) ng/L, P<0.05], and the scores of c-kit and motilin receptor protein were increased ( P<0.05). Conclusions:Dahuangfuzi decoction can improve the intestinal motility of SAP rats by promoting the secretion of motilin, increasing the activity of ICC cells and the expression of motilin receptor.

Effect of electroacupuncture on calcium-activated chloride channel currents in interstitial cells of Cajal in rats with diabetic gastroparesis / 针灸推拿医学（英文版）

Objective: To investigate the mechanisms of electroacupuncture (EA) at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) in intervening diabetic gastroparesis (DGP) based on calcium-activated chloride channel. Methods: Forty Sprague-Dawley rats were randomly divided into four groups, including a normal control group (group A), a model group (group B), an EA group (group C) and a metoclopramide group (group D), with 10 rats in each group. A single intraperitoneal injection of 2％ streptozotocin (STZ) combined with 8-week high-glucose high-fat diet was used to establish a DGP rat model. After intervention, gastrointestinal propulsive rate was observed; the expression level of transmembrane protein 16A (TMEM16A) was examined by immunohistochemistry; the Ca2+ concentration in interstitial cells of Cajal (ICCs) was detected by immunofluorescence; and whole-cell patch-clamp technique was applied to detect the current intensity of calcium-activated chloride channel (ICaCC) in ICCs in gastric antrum. Results: After modeling, the blood glucose levels in group B, group C and group D were significantly increased compared with group A (all P<0.01); after intervention, compared with group B, the blood glucose levels in group C and group D were significantly decreased (P<0.05, P<0.01); the intra-group comparison of blood glucose level between after modeling and after intervention found significant difference only in group C (P<0.01). The gastrointestinal propulsive rates in group B, group C and group D were significantly different from that in group A (P<0.01 or P<0.05); the gastrointestinal propulsive rates were markedly higher in group C and group D than in group B (P<0.01, P<0.01). The expressions of TMEM16A in group B and group C were decreased compared with group A (P<0.01, P<0.05); the expressions of TMEM16A in group C and group D were increased compared with group B (P<0.01, P<0.05). The fluorescence intensity of Ca2+ was significantly lower in group B than in group A (P<0.01); the fluorescence intensity of Ca2+ was significantly higher in group C and group D than in group B (P<0.01, P<0.05). ICaCC in ICCs in group B was significantly decreased compared with group A; ICaCC in group C and group D were increased compared with group B. Conclusion: EA at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) can significantly improve gastrointestinal motility in DGP rats by up-regulating the ICaCC in ICCs.

Role of Jiawei Shenqi-wan in Treatment of Cathartic Colon on the Basis of Interstitial Cells of Cajal / 胃肠病学

Background: Cathartic colon belongs to the category of 'constipation' in Traditional Chinese Medicine, and its pathogenesis is related to deficiency of kidney temperament and weak promotion ability, which has become a hot spot of global medical attention. Aims: To investigate the effect and possible mechanism of Jiawei Shenqi-wan (JSQW) on intestinal transmission function and pathological changes of interstitial cells of Cajal (ICCs) in rats with cathartic colon. Methods: Forty rats were randomly divided into blank group, model group, prucalopride group and JSQW group. Fecal moisture content, fecal particle number and intestinal transit rate were detected. The pathological changes of ICCs were observed under transmission electron microscope. RT-qPCR was used to detect the mRNA expressions of water channel proteins (AQP3 and AQP9) and SCF/c-kit pathway. Immunohistochemistry was used to measure the expressions of α-smooth muscle actin (α-SMA), inducible nitric oxide synthase (iNOS) and 5-hydroxytryptamine (5-HT)

Efficacy of Zhizhuwan Decoction and Its Ingredient-contained Serums on Proliferation and Apoptosis of Rat Colon Interstitial Cells of Cajal / 中国实验方剂学杂志

Objective:To explore the efficacy and molecular mechanism of Zhizhuwan decoction and its ingredient-contained serums on the proliferation and apoptosis of rat colon interstitial cells of cajal (ICC), and make a molecule-level analysis of the possible mechanism of traditional Chinese medicine (TCM) purgation-tonifying therapy in treating slow transit constipation (STC). Method:A total of 40 rats were divided into Atractylodis Macrocephalae Rhizoma(AMR) group, Aurantii Fructus Immaturus（AFI） group, Zhizhuwan group and blank serum group on random basis, with 10 in each group. Baizhu group was given 17.7 g·kg-1·d-1 of AMR decoction by gavage, AFI group was given 8.9 g·kg-1·d-1 AFI decoction by gavage, Zhizhuwan group was given 26.4 g·kg-1·d-1 Zhizhuwan decoction by gavage, and blank serum group was given 3 mL sterile distilled water for 7 consecutive days, once a day. Drug-contained serums and blank serum were collected from blood of the above groups and diluted to 5%, 10%, 15% and 20% concentrations. Each concentration was intervened for 24 h and 48 h, and the amount and status of ICC were observed. The best intervening concentration and time for each group with cell counting kit-8 (CCK-8) were determined. Rat colon ICC was divided into blank control group, blank serum group, AMR group, AFI group and Zhizhuwan group. ICC proliferation for each group was detected with EdU, ICC apoptosis for each group was detected by flow cytometry, and expressions of X-linked inhibitor of apoptosis protein (XIAP) and proliferating cell nuclear antigen (PCNA) were detected by Western blot. Result:Compared with the normal group, the best intervention concentration for blank serum group, AMR group and AFI group was 10%, while that for Zhizhuwan group was 5%. The best intervention times for the above groups were all 24 h. No distinct difference between the effect of blank control group and blank serum group on the proliferation and apoptosis of ICC was observed. In comparison with blank control group and blank serum group, AMR group, AFI group and Zhizhuwan group showed significant changes in ICC proliferation rate (P<0.05，P<0.01). There was a greater increase in ICC proliferation rate of Zhizhuwan group than that of AMR group and Zhizhu group (P<0.05，P<0.01), with no distinct difference between the changes of ICC proliferation rates in AMR group and AFI group. There was no significant difference between the changes of ICC apoptosis rates in AMR group, AFI group and Zhizhuwan group than in blank control group and blank serum group. There were significant increases in the expressions of XIAP and PCNA in AMR group, AFI group and Zhizhuwan group than in blank control group and blank serum group (P<0.05，P<0.01)， but with little difference among the three groups. Conclusion:At certain concentrations, Zhizhuwan, AFI and AMR all have the effect in improving ICC proliferation by increasing XIAP and PCNA expressions, with no evident effect on the apoptosis of ICC, based on TCM purgation-tonifying therapy, Zhizhuwan has the effect in improving ICC proliferation, with a better effect than single administration with AFI or AMR.

Colonic Transit Disorder Mediated by Downregulation of Interstitial Cells of Cajal/Anoctamin-1 in Dextran Sodium Sulfate-induced Colitis Mice

BACKGROUND/AIMS: Interstitial cells of Cajal (ICC) and their special calcium-activated chloride channel, anoctamin-1 (ANO1) play pivotal roles in regulating colonic transit. This study is designed to investigate the role of ICC and the ANO1 channel in colonic transit disorder in dextran sodium sulfate (DSS)-treated colitis mice. METHODS: Colonic transit experiment, colonic migrating motor complexes (CMMCs), smooth muscle spontaneous contractile experiments, intracellular electrical recordings, western blotting analysis, and quantitative polymerase chain reaction were applied in this study. RESULTS: The mRNA and protein expressions of c-KIT and ANO1 channels were significantly decreased in the colons of DSS-colitis mice. The colonic artificial fecal-pellet transit experiment in vitro was significantly delayed in DSS-colitis mice. The CMMCs and smooth muscle spontaneous contractions were significantly decreased by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), an ANO1 channel blocker, and NG-Nitro-L-arginine methyl ester hydrochloride (L-NAME), an inhibitor of nitric oxide synthase activity, in DSS-colitis mice compared with that of control mice. Intracellular electrical recordings showed that the amplitude of NPPB-induced hyperpolarization was more positive in DSS-colitis mice. The electric field stimulation-elicited nitric-dependent slow inhibitory junctional potentials were also more positive in DSS-colitis mice than those of control mice. CONCLUSION: The results suggest that colonic transit disorder is mediated via downregulation of the nitric oxide/ICC/ANO1 signalling pathway in DSS-colitis mice.

High-resolution Mapping of Hyperglycemia-induced Gastric Slow Wave Dysrhythmias

BACKGROUND/AIMS: It is now recognised that gastric dysrhythmias are best characterised by their spatial propagation pattern. Hyperglycemia is an important cause of gastric slow wave dysrhythmia, however, the spatiotemporal patterns of dysrhythmias in this context have not been investigated. This study aims to investigate the relationship between hyperglycemia and the patterns of dysrhythmias by employing high-resolution (multi-electrode) mapping simultaneously at the anterior and posterior gastric serosa. METHODS: High-resolution mapping (8 × 16 electrodes per serosal) was performed in 4 anesthetized hounds. Baseline recordings (21 ± 8 minutes) were followed by intravenous injection of glucagon (0.5 mg per dose) and further recordings (59 ± 15 minutes). Blood glucose levels were monitored manually using a glucose sensing kit at regular 5-minute intervals. Slow wave activation maps, amplitudes, velocity, anisotropic ratio, and frequency were calculated. Differences were compared between baseline and post glucagon injection. RESULTS: Baseline slow waves propagated symmetrically and antegrade. The blood glucose levels were increased by an average of 112% compared to the baseline by the end of the recordings. All subjects demonstrated elevated incidence of slow wave dysrhythmias following injection compared to the baseline (48 ± 23% vs 6 ± 4%, P < 0.05). Dysrhythmias arose simultaneously or independently on anterior and posterior serosa. Spatial dysrhythmias occurred before and persisted after the onset and disappearance of temporal dysrhythmias. CONCLUSIONS: Infusion of glucagon induced gastric slow wave dysrhythmias, which occurred across a heterogeneous range of patterns and frequencies. The spatial dysrhythmias of gastric slow waves were shown to be more prevalent and persisted over a longer period of time compared to the temporal dysrhythmias.

Control of Motility in the Internal Anal Sphincter

The internal anal sphincter (IAS) plays an important role in the maintenance of fecal continence since it generates tone and is responsible for > 70% of resting anal pressure. During normal defecation the IAS relaxes. Historically, tone generation in gastrointestinal muscles was attributed to mechanisms arising directly from smooth muscle cells, ie, myogenic activity. However, slow waves are now known to play a fundamental role in regulating gastrointestinal motility and these electrical events are generated by the interstitial cells of Cajal. Recently, interstitial cells of Cajal, as well as slow waves, have also been identified in the IAS making them viable candidates for tone generation. In this review we discuss four different mechanisms that likely contribute to tone generation in the IAS. Three of these involve membrane potential, L-type Ca²⁺ channels and electromechanical coupling (ie, summation of asynchronous phasic activity, partial tetanus, and window current), whereas the fourth involves the regulation of myofilament Ca²⁺ sensitivity. Contractile activity in the IAS is also modulated by sympathetic motor neurons that significantly increase tone and anal pressure, as well as inhibitory motor neurons (particularly nitrergic and vasoactive intestinal peptidergic) that abolish contraction and assist with normal defecation. Alterations in IAS motility are associated with disorders such as fecal incontinence and anal fissures that significantly decrease the quality of life. Understanding in greater detail how tone is regulated in the IAS is important for developing more effective treatment strategies for these debilitating defecation disorders.

Colonic Dysmotility in Murine Partial Colonic Obstruction Due to Functional Changes in Interstitial Cells

BACKGROUND/AIMS: Interstitial cells play important roles in gastrointestinal (GI) neuro-smooth muscle transmission. The underlying mechanisms of colonic dysmotility have not been well illustrated. We established a partial colon obstruction (PCO) mouse model to investigate the changes of interstitial cells and the correlation with colonic motility. METHODS: Western blot technique was employed to observe the protein expressions of Kit, platelet-derived growth factor receptor-α (Pdgfra), Ca²⁺-activated Cl⁻ (Ano1) channels, and small conductance Ca²⁺- activated K⁺ (SK) channels. Colonic migrating motor complexes (CMMCs) and isometric force measurements were employed in control mice and PCO mice. RESULTS: PCO mice showed distended abdomen and feces excretion was significantly reduced. Anatomically, the colon above the obstructive silicone ring was obviously dilated. Kit and Ano1 proteins in the colonic smooth muscle layer of the PCO colons were significantly decreased, while the expression of Pdgfra and SK3 proteins were significantly increased. The effects of a nitric oxide synthase inhibitor (L-NAME) and an Ano1 channel inhibitor (NPPB) on CMMC and colonic spontaneous contractions were decreased in the proximal and distal colons of PCO mice. The SK agonist, CyPPA and antagonist, apamin in PCO mice showed more effect to the CMMCs and colonic smooth muscle contractions. CONCLUSIONS: Colonic transit disorder may be due to the downregulation of the Kit and Ano1 channels and the upregulation of SK3 channels in platelet-derived growth factor receptor-α positive (PDGFRα⁺) cells. The imbalance between interstitial cells of Cajal-Ano1 and PDGFRα-SK3 distribution might be a potential reason for the colonic dysmotility.

Effect of Houpu Sanwu Tang on Small Intestine Interstitial Cells of Cajal and iNOS in Postoperative Ileus Rats / 中国实验方剂学杂志

Objective: To evaluate the effect of Houpu Sanwu Tang on the postoperative ileus (POI), and observe its underlying mechanisms of action on interstitial cells of cajal (ICC) and inducible nitric oxide synthase(iNOS) regulation of POI. Method: Totally 87 healthy adult male SD rats were randomly divided into sham operation group, saline control group and Houpu Sanwu Tang group at low, medium and high doses. Houpu Sanwu Tang low, middle and high dose groups received orally Houpu Sanwu Tang(2.25,4.5,9 g·kg-1); Sham operation group (Sham operation) and saline control group (Saline control) received orally normal saline. Surgical procedure was used to induce the postoperative ileus. Changes in intestinal propulsion rate, intestinal mucosal injury and small intestine expression of c-kit and iNOS among these groups were detected. Result: Intestinal propulsion rate was significantly higher in Houpo Sanwu Tang group than that in Saline control group (PPPPConclusion: Houpu Sanwu Tang can improve the intestinal propulsion rate and the recovery in POI rats. The mechanisms are related to the inhibition of the generation of iNOS, the alleviation of inflammatory response, and increase of the number of ICC, so as to ensure its normal function, and improve the intestinal dynamic disorder.