胃肠舒对糖尿病胃轻瘫大鼠胃窦Cajal间质细胞病变的影响

目的:研究胃肠舒和血流干预药物对糖尿病胃轻瘫大鼠胃窦Cajal间质细胞(ICC)病变的影响。方法:131只SPF级SD雄性大鼠,随机分为正常组、模型组、止血敏组、蚓激酶组和胃肠舒组;除正常组外大鼠一次性腹腔注射链脲佐菌素造模。30周后检测血糖、FINS、C-P、胃液体排空率等指标。取胃窦组织行免疫组化染色,光镜下观察胃窦ICC的数量,计数nNOS阳性神经元。电镜下观察胃窦ICC超微结构改变。结果:30周后模型组大鼠胃窦部ICC数量减少、肌间神经丛nNOs阳性神经元减少、细胞变性。经胃肠舒和蚓激酶治疗后大鼠胃窦部ICC的病理损害减轻,可见ICC的数量明显增多、细胞间的连接增多。而用止血敏干预的大鼠胃窦部ICC的病理损害加重,表现为ICC的数量更少、细胞间的连接显著减少,尚存的细胞间连接的结构也有破坏,结构不清,连接松散。结论:胃肠舒具有降糖、改善胃窦Cajal间质细胞病变、促进胃动力的作用。

半夏泻心汤合穴位注射治疗2型糖尿病胃轻瘫40例

目的:观察半夏泻心汤合穴位注射治疗2型糖尿病胃轻瘫的疗效。方法:选取糖尿病胃轻瘫患者80例,随机分为治疗组与对照组,分别予半夏泻心汤加减联合维生素B12足三里穴位注射和单纯予多潘立酮口服治疗,观察2组疗效差异。结果:治疗组治愈、好转及无效例数分别为12、22、和6,对照组治愈、好转及无效例数分别为10、20和10。结论:半夏泻心汤联合维生素B12足三里穴位注射治疗2型糖尿病胃轻瘫疗效显著。

Gastroparesis: Current diagnostic challenges and management considerations

Gastroparesis refers to abnormal gastric motility characterized by delayed gastric emptying in the absence of mechanical obstruction. The most common etiologies include diabetes, post-surgical and idiopathic. The most common symptoms are nausea, vomiting and epigastric pain. Gastroparesis is estimated to affect 4% of the population and symptomatology may range from little effect on daily activity to severe disability and frequent hospitalizations. The gold standard of diagnosis is solid meal gastric scintigraphy. Treatment is multimodal and includes dietary modification, prokinetic and anti-emetic medications, and surgical interventions. New advances in drug therapy, and gastric electrical stimulation techniques have been introduced and might provide new hope to patients with refractory gastroparesis. In this comprehensive review, we discuss gastroparesis with emphasis on the latest developments; from the perspective of the practicing clinician.

Effect of Electroacupuncture on Platelet-derived Growth Factor and the Ultrastructure of Mitochondria in Rats with Diabetic Gastroparesis

Objective To observe the effect of electroacupuncture(EA)at the pressure points Zu San Li(ST36),San Yin Jiao(SP6)and Liang Men(ST21)on platelet-derived growth factor(PDGF)and the ultrastructure of mitochondria in rats with diabetic gastroparesis(DGP).Methods Sixty Sprague Dawley(SD)rats were randomly separated into a normal control group(NC,n=10)and a modeling group(n=50).Rats in the modeling group received an injection of 2%streptozotocin(STZ)and a high-fat and highglucose diet for eight weeks to establish a DGP rat model.At the same time,blood glucose and a general symptom score were recorded every week.After modeling,30 successfully modeled rats were randomly separated into the following groups:the DGP group(n=10),the EA group(n=10)and the metoclopramide(MP)group(n=10).After three weeks of intervention,the gastrointestinal propulsive rate was measured by measuring the optical density(OD).The concentration of Ca2+was determined by fluorescence immunoassay,and levels of serum insulin(INS)and PDGF were determined by ELISA.The ultrastructure of mitochondria was observed with transmission electron microscopy.Results(1)After intervention,levels of blood glucose and the general symptom score were greatly decreased in the EA group compared to the DGP group(P<0.01).Compared with the DGP group,the gastric emptying rate and the intestinal propulsive rate of the EA group was significantly improved(P<0.01),and there was no statistically significant difference between the EA and the NC groups.(2)Compared with the NC group,the levels of INS in the DGP group markedly decreased(P<0.05),but there was no significant difference of INS levels between the EA and the MP roups.(3)Compared with the DGP group,theconcentration of Ca2+in the EA and the MP groups significantly increased(P<0.01,P<0.05,respectively).(4)Compared with the NC group,the average OD of PDGF in the DGP group was significantly higher(P<0.01).Compared with the DGP group,levels of PDGF in the EA group increased significantly(P<0.01).(5)There were abundant mitochondria with a clear structure and complete cristae in the NC group.However,in the DGP group,mitochondria were severely swollen,partly vacuolated,and cristae were either fractured,absent,or shortened.In the EA group,mitochondria were slightly swollen,with clear cristae.Conclusions Electroacupuncture at the points Zu San Li(ST36),San Yin Jiao(SP6)and Liang Men(ST21)may improve gastric motility in DGP by up-regulating the amount of PDGF and improving the ultrastructure of mitochondria.

A meta-analysis of Wendan decoction in the treatment of diabetic gastroparesis

Objective To evaluate the clinical efficacy and safety of Wendan decoction in the treatment of diabetic gastroparesis (DGP). Methods PubMed, MEDLINE, The Cochrane Library, Embase, China Biology Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP) and Wanfang databases were searched and eligible randomized controlled clinical trials (RCTs) were included. The quality of the RCTs was evaluated by the Cochrane risk of bias assessment tool, and data analysis were performed with Review Manager 5.3. Results A total of 7 studies were included, including 533 patients. Meta analysis results showed that the effective rate of Wendan decoction in the treatment of diabetic gastroparesis was better than that of the control group [RR=1.30, 95%CI (1.20, 1.40), P<0.001], and the improvement of fasting blood glucose (FBG) was better than that of western medicine [MD =-0.43, 95%CI (-0.91,-0.01), P=0.05]. The recurrence rate in the TCM treatment group was lower than that in the western medicine group[RR = 0.29, 95%CI (0.13, 0.62), P=0.002]. Conclusion Compared with western medicine, Wendan decoction has better curative effect on DGP and can reduce its recurrence rate. However, due to the low quality of the included literatures and the possibility of bias, large-scale and high-quality RCTs are still needed for further confirmation.

Effect of acupuncture combined with Chinese medicine on the expression of interstitial cells of Cajal, substance P and nerve nitric oxide synthase in diabetic mice with gastroparesis antrum

Objective To explore the effect of acupuncture combined with Chinese medicine on expression of interstitial cells of Cajal（ICC）, substance P（SP） and nerve nitric oxide synthase（nNOS） in diabetic gastroparesis mice. Methods Eighty Kunming male mice were randomly divided into normal group（group A, 15 mice）, diabetic gastroparesis model mice group（group B, 12 mice）, acupuncture combined with Chinese medicine group（group C, 12 mice）, Chinese medicine group（group D, 13 mice） and western medicine group（group E, 13 mice）. The mice were intraperitoneally injected with steptozotocin and fed with high-fat diet-induced irregular except the normal group mice, that made mouse model of diabetic gastroparesis. And then, the ACM group were treated by acupuncture at the acupoints of Housanli（后三里 ST 36） and Zhōngw n（中脘 CV 12） combined with Chinese medicine, the CM group were only treated by Chinese medicine; the WM group were treated by domperidone and vitamin B 6. Numbers and expression of ICC, SP and n NOS were detected by immunohistochemical methods. Results After treatment, compared with normal group, ICC and SP indexes of model group were significantly reduced. Compared with model group, all indexes in ACM and CM groups were improved significantly（P0.05, P0.01）, but only the positive area and average optical density value in c-Kit and SP in WM group increased obviously（P0.05）. Compared with ACM group, no significant difference in c-Kit and SP of CM group were observed（P0.05）, but expression of nNOS were increased markedly（P0.01）. Besides, c-Kit and SP expressions of WM group were significantly induced was increased remarkably（P0.01）. Conclusion Acupuncture combined with Chinese medicine have much better therapeutic effects for diabetic gastroparesis mice, which may be due to repairing ICC damage, upregulating the expression of SP and lowering the expression of nNOS.

Study on the mechanisms of electroacupuncture for promoting gastrointestinal motility in rats with diabetic gastroparesis

Objective： To observe the effect of electroacupuncture（EA） at Zusanli（ST 36） on the gastrointestinal motility and the ultrastructures of pacemaker cells [the interstitial cells of Cajal（ICC）] in diabetic gastroparesis（DGP） rats and explore the mechanism of EA for DGP.Methods： A total of 50 Sprague-Dawley（SD） rats were randomly divided into group A, group B, group C, group D and group E, with 10 rats in each group. Group A was the blank control; a single intraperitoneal injection of 2% streptozotocin（STZ） was performed in rats of group B, group C, group D and group E, with high glucose and high fat diet for 8 weeks to establish the DGP rat models. Group B was the model group and the rats did not receive any treatment; group C was EA at acupoint group and the rats received EA at Zusanli（ST 36）, Liangmen（ST 21） and Sanyinjiao（SP 6）; group D was EA at non-acupoint group and the rats received EA at the control points of Zusanli（ST 36）, Liangmen（ST 21） and Sanyinjiao（SP 6）; group E was metoclopramide group and the rats were treated by intragastric administration of metoclopramide. Blood glucose was detected using ONE TOUCH blood glucose meter; gastric emptying rate and small intestine migration rate were measured using intragastric phenol red; ultrastructures of gastric antrum ICC were detected by transmission electron microscopy. Results： The differences of blood glucose between group B, group C, group D, group E versus that of group A were statistically significant after modeling（P〈0.01）; after treatment, the differences of blood glucose between group D, group E versus that of group C were statistically significant（P〈0.05, P〈0.01）; the gastric emptying rate of rats in group B was statistically significant different from that in group A（P〈0.01）; the gastric emptying rate of rats in group C was statistically significant different from that in group B（P〈0.01）. The migration rates of rats＇ small intestines in group B, group C, group D and group E were all statistically significant different from that in group A（P〈0.01）; the migration rate of rats＇ small intestines in group C was statistically significant different from that in group B（P〈0.01）. The ultrastructure of rat＇s ICC in group B showed apoptosis compared with that in group A; rat‘s ICC in group C had complete basement membrane, more cytoplasm mitochondria, Golgi and rough endoplasmic reticulum, showing clear structure, occasional mitochondria swelling and gap junctions with adjacent smooth muscle cells; there were no significant differences between group D, group E versus group B. Conclusion： EA at Zusanli（ST 36） plus other acupoints can regulate the blood glucose and promote gastrointestinal motility in DGP rats, and the mechanism may be related to repairing the damaged ICC structure.

Effect of electroacupuncture on electrogastrogram and gastric antrum ghrelin in rats with diabetic gastroparesis

Objective： To observe the effect of electroacupuncture（EA） on the electrogastrogram and gastric antrum ghrelin in rats with diabetic gastroparesis（DGP）.Methods： Fifty Sprague-Dawley（SD） rats were randomly divided into group A, group B, group C, group D and group E,10 rats in each group. Group A was the blank control group without intervention. Group B, Group C, Group D and Group E were treated with single dose intraperitoneal injection of 2% streptozotocin（STZ）, combined with 8-week high glucose and high fat diet to establish DGP rat models. Group B was the model group without treatment. Group C was the EA at acupoint group, was treated with EA at Zusanli（ST 36）, Liangmen（ST 21） and Sanyinjiao（SP 6）. Group D was the EA at non-acupoint group, was treated by EA at the control points of Zusanli（ST 36）, Liangmen（ST 21） and Sanyinjiao（SP 6）. Rats in the metoclopramide control group received 1.7% metoclopramide solution [10 mL/（kg·bw）] by gavage. Rat＇s blood glucose level was measured by blood glucose meter; gastric emptying rate was detected using phenol red as a marker; the electrogastrogram was detected by BL-420 F biological function system; the protein level of ghrelin was detected by enzyme-linked immunosorbent assay（ELISA）; the expression of ghrelin mRNA was detected by real-time polymerase chain reaction（RT-PCR）.Results： Compared with group A, the blood glucose of group B, C, D and E were significantly increased before and after the treatment（all P〈0.01）; after treatment, the gastric emptying rate of group B was significantly decreased（P〈0.01）,the migration rates of small intestine in group B, C, D and E were significantly lower（all P〈0.01）, and the protein content of ghrelin in group C was significantly decreased（P〈0.01）; the expressions of ghrelin mRNA were significantly increased in group B, C, D and E（all P〈0.01）, the mean amplitudes of electrogastrogram in group B and D were significantly decreased（both P〈0.01）. After treatment, compared with group B, the blood glucose of group C was significantly decreased（P〈0.05）, the gastric emptying rate and small intestine migration rate were significantly increased in group C and E（P〈0.05, P〈0.01）, the small intestinal migration rate was significantly increased in group D（P〈0.05）, the expression of ghrelin in protein and mRNA in group C was significantly lower（P〈0.01）, the expression of ghrelin mRNA in group E was significantly lower（P〈0.05）, and the mean amplitude of electrogastrogram in group C was significantly increased（P〈0.05）. After treatment, compared with group D, the protein and mRNA expressions of ghrelin in group C were significantly decreased（P〈0.01）. After treatment, compared with group E, the protein expression of ghrelin in group C was significantly decreased（P〈0.01）.Conclusion： EA at Zusanli（ST 36）, Liangmen（ST 21） and Sanyinjiao（SP 6） could regulate the blood glucose level of DGP model rats, enhance electrogastrogram activity, promote gastric emptying, and regulate ghrelin expression in protein and mRNA.

Effect of electroacupuncture on gastric motility, expressions of ghrelin and GHSR mRNA in gastric antrum tissue of diabetic gastroparesis rats

Objective： To explore the action mechanism of electroacupuncture （EA） in improving the gastric motility of rats with diabetic gastroparesis （DGP）. Methods： Forty-eight healthy Sprague-Dawley （SD） rats were randomly assigned into four groups： a normal group （group A）, a model group （group B）, a group of EA at acupoints （group C）, and a group of EA at non-acupoints （group D）, 12 rats in each group. The animal model of DGP was established by intraperitoneal injection of streptozotocin （STZ） plus high glucose and fat diet. The blood glucose, urine glucose and gastric emptying rate （GER） were observed. The content of insulin （INS） in serum and ghrelin in gastric antrum tissue were detected by enzyme linked immunoassay （ELISA）. The expression of growth hormone secretagogue receptor mRNA （GHSR mRNA） in gastric antrum tissue was detected by real-time fluorescent quantitative polymerase chain reaction （PCR）. Results：Compared with group A, blood glucose and urine glucose increased significantly （P〈0.01）, GER, content of serum insulin, the content of ghrelin and expression of GHSR mRNA in gastric antrum tissue decreased significantly （P〈0.05 orP〈0.01） in group B. Compared with group B, blood glucose and urine glucose decreased significantly （P〈0.05）, GER, the content of insulin in serum, the content of ghrelin and expression of GHSR mRNA in gastric antrum tissue increased significantly （P〈0.05 orP〈0.01） in group C. Conclusion： EA at acupoints can down-regulate the content of blood and urine sugar, and promote gastric emptying, which is possibly related to the regulation of serum insulin, and the expressions of ghrelin and GHSR mRNA in gastric antrum.

Efficacy observation on acupuncture for diabetic gastroparesis

Objective： To observe the effect of acupuncture on gastric motility, plasma motilin and serum gastrin in patients with diabetic gastroparesis （DGP） and evaluate its clinical efficacy. Methods： A total of 100 eligible cases were randomly allocated into an acupuncture group （n=50） and a control group （n=50）. Patients in the acupuncture group were treated by needling Zhongwan （CV 12）, Zusanli （ST 36） and Neiguan （PC 6）, whereas patients in the control group were treated with oral administration of Domperidone. The clinical efficacies of the two groups were compared; and changes in gastric motility, plasma motilin and serum gastrin in both groups were observed before and after treatment. Results： After treatment, the symptom scores, gastric motility and contents of plasma motilin and serum gastrin were significantly improved in both groups （P〈0.05）. There were between-group statistically significant differences in symptom scores, gastric motility and levels of plasma motilin and serum gastrin after treatment （all P〈0.05）. The total effective rate was 96% in the treatment group, versus 78% in the control group, showing a statistically significant difference （P〈0.05）. Conclusion： Acupuncture is effective for DGP and can reduce the levels of plasma motilin and serum gastrin.

Clinical Observation on the Treatment of Diabetic Gastroparesis with Acupuncture

Objective： This study was to observe the therapeutic effect of acupuncture in the treatment of diabetic gastroparesis. Methods： Ninety patients with diabetic gastroparesis were randomly allocated into 2 groups, a treatment group （45 subjects） to receive acupuncture treatment, and a control group （45 subjects） to take domperidone tablet. Results： Four treatment courses later,the total effective rate was 91.1% in the treatment group and 64.4% in the control group, and the difference was statistically significant （P〈0.05）. Conclusion： The diabetic gastroparesis responds wellto acupuncture treatment.

Effect of electroacupuncture on calcium-activated chloride channel currents in interstitial cells of Cajal in rats with diabetic gastroparesis

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.

Effect of acupuncture at points selected from different regions on SCF-kit signaling pathway in diabetic gastroparesis rats

Objective： To observe the effect of acupuncture at points selected from different regions on the positive expression of interstitial cells of Cajal （ICC） and the stem cell factor （SCF） in gastric antrum tissues in diabetic gastroparesis （DGP） rats, and to explore the influence of region-based point selection on the acupoint combination efficacy. Methods： Sixty Sprague-Dawley （SD） rats were randomly divided into a normal group （group A）, a model group （group B）, a group of Zusanli （ST 36） plus Zhongwan （CV 12） （group C）, a group of Zusanli （ST 36） plus Neiguan （PC 6） （group D）, and a group of Zusanli （ST 36） plus non-meridian non-acupoint points （group E）, based on the random number table （n=12）. DGP rat model was established by single intraperitoneal injection of 2% streptozotocin and common diet. After successful modeling, the rats were treated once a day for 4 weeks. Positive ICC and SCF expressions were measured by immunohistochemistry. Results： Compared with group A, the gastrointestinal propulsion rate of group B showed a statistically significant decrease （P〈0.05）. Compared with group B, the gastrointestinal propulsion rate and the expression of ICC in the gastric antrum were significantly higher in group C, group D and group E, and the between-group differences were statistically significant （P〈0.05）; the expression of C-kit protein in group C was statistically significantly higher than that in group D and group E （P〈0.05）. The expression of SCF protein was significantly increased in group C than in group B, and the difference was statistically significant （P〈0.05）. Conclusion： Acupuncture can improve the symptoms of delayed gastric emptying in DGP model rats, and regulate the expression of ICC and SCF in gastric antrum tissues. The effect of Zusanli （ST 36） plus Zhongwan （CV 12） in the gastric region is superior to that of the Zusanli （ST 36） plus distal Neiguan （PC 6） or non-meridian non-acupoint point, indicating that region-based point selection is the key factor affecting the effect of acupoint combination.

Effect of point-moxibustion on ghrelin and GHSR-1a expressions in lateral septal nucleus of rats with diabetic gastroparesis

Objective： To observe the effect of point-moxibustion on gastrointestinal motility, mRNA and protein expressions of ghrelin and growth hormone secretagogue receptor la （GHSR-la） in lateral septal nucleus of rats with diabetic 8astroparesis （DGP）, and to investigate the central regulatory mechanism of DGP treatment with point-moxibustion. Methods： Forty SPF-grade Sprague-Dawley （SD） rats were randomly divided into a blank group, a model group, an electroacupuncture （EA） group and a point-moxibustion group, with 10 rats in each group. A DGP rat model was established by intraperitoneal injection of 2% streptozotocin （STZ） with 8-week irregular high-sugar and high-fat diet in the model group, the EA group and the point-moxibustion group, and rats in the blank group were injected intraperitoneally with 0.1 mmoL/L （pH 4.5） citric acid-sodium citrate buffer with 8-week normal diet. Eight weeks later, rats in the EA group were treated by EA at Zusanli （ST 36）, Liangmen （ST 21） and Sanyinjiao （SP 6）; while rats in the point-moxibustion group were treated by point-moxibustion at Zusanli （ST 36）, Liangmen （ST 21） and Sanyinjiao （SP 6） for successive 15 d. Rats in the blank group and the model group were fixed as the control without intervention. After treatment, intestinal propulsion rate and gastric emptying rate were measured. The mRNA and protein expressions of ghrelin and GHSR-la in the lateral septal nucleus were detected by real-time polymerase chain reaction （RT-PCR） and Western blot （WB）. Results： Compared with the blank group, the intestinal propulsion rate and gastric emptying rate of the model group were significantly lower （both P〈0.01）; compared with the model group, the intestinal propulsion rate and gastric emptying rate of the EA group and the point-moxibustion group increased significantly （all P〈0.05）. The mRNA and protein expressions of ghrelin and GHSR-la were lower in the model group than those in the blank group （all P〈0.01）. The mRNA and protein expressions of ghrelin and GHSR-Ia were significantly higher in the EA group and the point-moxibustion group than those in the model group （all P〈0.05）. There were no statistically significant differences between the EA group and the point-moxibustion group （all P〉0.05）. Conclusion： Point-moxibustion at Zusanli （ST 36）, Liangmen （ST 21） and Sanyinjiao （SP 6） can increase the intestinal propulsion rate and gastric emptying rate of DGP rats, and promote the mRNA and protein expressions of ghrelin and GHSR-la in the central nervous system. The mechanism may be related to the activation of 8hrelin pathway in hypothalamic arcuate nucleus-lateral septal nucleus.