Effect Of Electro-Acupuncture In Treating Diabetic Gastroparesis And Gastric Motility Studies

Diabetic gastroparesis (diabetic gastroparesis DGP) is one of the chronic complications of diabetes mellitus. The primary pathological changes are low tension of gastric sinus, movement weakened and slow, emptying delay, food stasis within the gastric antrum, and upper gastrointestinal discomfort symptoms. Acupuncture has some advantages in the treatment of diabetic gastroparesis, because of simple, convenient, effect and inexpensive.It can not only cure or improve symptoms of gastroparesis, but also taking into account of the hypoglycemic, playing a double role. Study on the plasticity of gastrointestinal function in recent years for the recovery of gastrointestinal function after diabetic gastroparesis opened a new research direction, while the ICC is the most relevant gastrointestinal cells to reflect the gastrointestinal reconstruction as pacemaker cells. Therefore, this article intent to further reveal the mechanism of electro-acupuncture in treating diabetic gastroparesis by studying on the effect of electro-acupuncture on diabetic gastroparesis and gastric dynamic role, provide a solid theoretical foundation for clinical treatment. This article is divided into four parts:literature research, clinical researc, experimental research and conclusion.1. Literature researchThrough the research to the theory of etiology and pathogenesis of GDP on ancient and modern literature, we believe that TCM of diabetic gastroparesis are "PI Syndrome" category, its pathogenesis is primarily dysfunction of the spleen in transportation and transformation, failure of stomach-qi to descend, its position mainly in the stomach. This article carried out a review on modern medicine to gastrointestinal motility disorders and ICC, then believed that the pathogenesis of gastrointestinal motility disorder may be autonomic nervous dysfunction, gastrointestinal hormone secretion exceptions, Hyperglycemia, muscle damage, microvascular disease and other factors combined impact results. In addition, the interstitial cells of Cajal(ICC)damage or dysfunction may also be one of the mechanisms of diabetic gastrointestinal motility disorders, and electro-acupuncture can cure or improve symptoms of gastroparesis, while taking into account of the hypoglycemic, plays an important role on gastrointestinal motility and function remodeling.2. Clinical researchPurposeTo study on effect of electro-acupuncture in treating DGP and gastric motility, by a prospective randomized method. Looking for effective methods of treatment of DGP, improving the DGP gastric sinus in patients with tension and promote emptying of gastric contents, alleviating the clinical signs, thereby facilitating a better blood glucose control, reducing the incidence of serious complications.MethodsThe experimental study uses 60 patients meeting standard of DGP,30 of them were randomly selected as the EA group(I), the left 30 cases were made to control group(H); the EA group was for electric needle treatment while accepting general hypoglycemic agents, needling in RN12, and LR13(double), and BL21 (double), and BL20(double), and ST36(double), and ST25 (double), using electric needle in the first treatment days, stimulated with 15Hz wave of the same amplitude for 20 minutes once a day,5 days for one course,2 days off between each course,2 consecutive courses in all; H group for controlled group, given mosapride 5mg/tid,15-30 min before a meal orally, two week for a course. Used PI full grade, gastrointestinal symptom score, and fasting blood glucose as the therapeutic index, made an evaluation before and after treatment. The data will be established a database, applicating SPSS13.0 statistical software for statistical analysis.ResultsTreatment classification of two groups of patients with PI full pass before scoring, feeling of fullness card full stomach heave, glutted time, diet changes, stool, stomach pain, heat, clinical symptoms, such as scoring and fasting blood glucose, through statistical calculation,the differences were not statistically significant(P>0.05). After treatment, two groups of patients with PI full pass grade, full stomach heave, glutted time diet changes, stool, stomach pain, heat, scores are declining (P<0.01, P<0.05), and the treatment group than the control group (P<0.01, P<0.05), two sets of fasting blood glucose is falling (P<0.01), in which the fasting blood glucose, no significant differences between the two groups (P>0.05). Comparison of the two groups, after Ridit analysis, P<0.05, statistically significant differences, effect of the two groups differ, effect better treatment group than the control group.Conclusion1. Electric needle and oral mosapride are on DGP patients PI full card and the gastrointestinal road symptoms has improve role, electric needle treatment more excellent; 2. Electric needle and oral mosapride are on DGP patients PI full card are has better effect, and electric needle treatment of cure degree more excellent; 3. Electric needle and oral mosapride treatment measures may by improve DGP patients gastric power obstacles and on fasting blood glucose reduce has must role.3. Experiments researchPurposeObservation of electroacupuncture on blood glucose in diabetic rats with gastroparesis and gastrointestinal tract motility and Ultrastructure changes of ICC cells of impact further revealed possible effects of electro-acupuncture in treating diabetic gastroparesis mechanism.MethodsSelect male SD·110 in rats, randomly divided into control group(25), the model group(25), the Western medicine group(25), electro-acupuncture Group(25). Model groups animals,55mg/kg weight loss chain pulse effect of adjuvant intraperitoneal injection at once, preparation of diabetic rat model, model successful diabetic model in rats after 10 weeks randomly divided into groups(DM), Western medicine group(DM+DRU), electro-acupuncture group (DM+ACU). Electro-acupuncture group needle treatment 1 times a day,5 days for a course, each course of 2 days, treatment of 4 courses; Western medicine group to the intragastric administration of mosapride,1 times a day,5 days for a course, each course of 2 days, treatment of 4 courses; blank treatment groups, model groups do nothing. Periodical observation records during experimental rats with diet, dung, activities such as the General status and blood sugar, weight. Experiment before the end of a day record weight and the tail vein of rat blood glucose values, and isotope detection. Late times electric needle Hou fasting 24 hours, the group are by mouth given 10% of carbon powder mixed suspended liquid (which activated carbon and Arab rubber the containing 10%), by 10ml/kg weight dosage irrigation gastric,30 minutes Hou will large rats cervical dislocated executed, open abdominal, by following formula calculation gastrointestinal promoting index:gastrointestinal promoting index=carbon powder front-end to Helicobacter pylori sphincter distance (cm)/Helicobacter pylori sphincter to intestinal end distance (cm) x 100%. Measurements taken after the completion of gastric antrum tissue of four blocks, a to-20°c refrigerators save standby, ELISA determination of gastrointestinal hormones; a place 10% fixed in formalin solution, do HE and immunohistochemical staining of c-Kit; a into a tank of liquid nitrogen,-70°c and low temperature refrigerator saves, done by fluorescence quantitative PCR detection of gene expression of c-Kit; a electron microscopic detection. Observe the following indicators:(1) Radionuclide scanning method to detect changes of gastric emptying of rats in each group.(2) Behavior of rats in each group (hair, heavy weight, manure, etc), and gastrointestinal blood sugar rate changes.(3) Detection by ELISA method respectively groups of rat gastric antrum and serum motilin and gastrin and somatostatin expressions.(4) HE dyeing and immunohistochemical observation of gastric antrum of rats in each group by ICC distribution of interstitial cells and morphological changes, using laser scanning confocal microscopy observation number of ICC stromal cells.(5) Transmission electron microscopic observation on ICC stromal cells of rats in each group of changes of ultrastructure and morphology.(6) Using fluorescent quantitative PCR method for observation of gastric antrum of rats in each group c-Kit changes of gene expression.(7) The application of statistical software SPSS13.0 do respectively groups of rat's gastrointestinal motility and functional gastrointestinal hormones, canonical correlation analysis of the ICC.Results(1) Changes in gastrointestinal motility disordersThe experiment results shows that there is significant difference (P<0.01) between the model group and control group in a blank set of half-row time in gastric emptying,60 minutes gastrointestinal rate and gastrointestinal propulsion rate, then it proved the animal models of diabetic gastroparesis success. In addition, there is also significant difference (P<0.01) between the EA group and model group in a blank set of half-row time in gastric emptying,60 minutes gastrointestinal rate and gastrointestinal propulsion rate, it shows acupuncture can promote gastric emptying rapidly.(2) Changes of behavior and the blood sugar levelBy observation of behavior, there are significantly differences between model group(Model group,Western medicine group and EA group) and controlled group in main syndrome "Three mores and one less", activities, reaction, hair growth, eating, urination and defecationl, weight, complications and the mortality rate; the symptoms have been reduced obviously in EA group comparing with model group and Western medicine group, the blood sugar level have been reduced obviously in EA group comparing with model group and Western medicine group.(3) Changes of gastrointestinal hormones and correlation analysisUnder normal circumstances, it can be seen from the control group that the content of MTL in the serum and gastric tissue is at a low level. But in pathological conditions, the content of MTL in serum and gastric tissue were increased to varying degrees by the model group, western medicine group and EA group. And there may be a negatively correlated relationship in the content of MTL in serum and in antral tissue.Under normal circumstances, it can be seen from the control group that the content of GAS in the serum and gastric tissue is at a low level. But in pathological conditions, the content of GAS in serum and gastric tissue were increased to varying degrees by the model group, western medicine group and EA group. And there may be a negatively correlated relationship in the content of GAS in serum and in antral tissue.Under normal circumstances, it can be seen from the control group that the content of SS in the serum and gastric tissue is at a low level. But in pathological conditions, the content of SS in serum and gastric tissue were increased to varying degrees by the model group, western medicine group and EA group. And there may be a negatively correlated relationship in the content of SS in serum and in antral tissue. (4) HE staining and immunohistochemistry resultsGastric tissue to groups of rats were observated under light microscope after HE staining. The result shows that:Rats mucosal glands and smooth muscle cells arranged in tight rules, moderate gap between cells, no va-cuolar degeneration, no vasodilation and so on in the control group;Gland malalignment, the cell gap becomes larger, the gland cell cytoplasm decreased, staining pale, vacuolar degeneration, mucous membrane and submucosa congestion, vasodilatation, gastric smooth muscle cytoplasm pale, translucent, with vacuoles degeneration in DGP model group;compared with model group, there are gastric mucosa and submucosa reduce vascular congestion, mucosal glands and smooth muscle cells arranged in neat, little vacuolation, cell gap slightly, a small amount of vacuolar degeneration in the stomach in the Western Medicine Group;compared with model group, there are gastric mucosal and submucosal vascular congestion mitigation, mucosal glands and smooth muscle cells arranged in neat, little vacuolation, cell gap slightly, a small amount of vacuolar degeneration in the stomach in the EA group.Image Analysis shows that the positive ICC content in rats of control group is maximum; there are significant differences (P<0.01) among contrlo group, model group and EA groups. Control group> EA group> Western medicine group> Model group. So electro-acupuncture can regulate positive of the ICC content in c-kit.c-kit after the immunohistochemical marker, under optical microscope observation to the ICC was dyed brown-yellow cell membrane and Cytoplasmic coloring. Control group of rats positive ICC in the gastric antrum is most intensive in circular muscle layers and longitudinal muscle layer between circular muscle cells and the inner surface of circular muscle layers, and particularly between the central longitudinal muscle, most of the cells and nerve fibers of peripheral nerve with and closely connected together by a number of GAP junction and clustered distributions. Mostly spindle cells, elongated or irregular in shape, have more processes, less cytoplasm, nucleus large, mostly oval, stained darker. Model group ICC was significantly reduced, cell shrinkage, disappearance processes, cell poor contrast, the tight junctions among ICC,nerve cells and smooth muscle cells was significantly reduced;Western Medicine Group reduce the number of ICC significantly, cell shrinkage, disappearance processes, cell poor contrast, the tight junctions among ICC,nerve cells and smooth muscle cells was significantly reduced;EA treatment group, the number of ICC decreased slightly, but basically normal morphology, neurite shortening, the close connection between ICC and the other cells exits.(5) Transmission electron microscope experiment resultsCompared with the control group, DGP model rats shows that the gap junctions among antrum ICC, other interstitial cells, smooth muscle cells and nerve endings were significantly reduced, the structure is damaged;significant reduction in the number of organelles;Cellular structure defects and pathological change significantly. The number of antral ICC in the EA group is more than the model group, slightly less than the control group. ICC morphology is basically normal, the mitochondria in it less than the control group, and mild swelling can be seen, the gap junctions between cells remained. Pathological damage of connections among ICC, smooth muscle cells and nerve is lighter than the model groups, and its structure clearer and close. Intramural nerve, distribution of ICC and the pathological damage of processes connection is also lighter than model group. Capillary wall of the stomach in rats is uneven, endothelial cell swelling and silting reduced, fewer vacuoles.(6) Fluorescence Quantitative PCR Detection resultsCompared with the control group, the kit expression in rats gastric tissue of all groups declined, differences are significant (P<0.01). The results show that Kit expression of the control group multiple) EA group> Western medicine group> model group, the four differences are statistically significant (P <0.05).(7) Linear regression and correlation analysis:ICC content and gastrointestinal hormones in.the organization of MTL and GAS make the most significant impact on changes of gastric motility parameters, while the glycemic index changes after treatment seems little correlation between changes in gastric motility. Because of electro—acupuncture intervention in diabetic gastroparesis and the changes of gastric motility parameters after ICC interstitial cell and gastrointestinal hormone of MTL and GAS, SS are closely related, electro-acupuncture promoting the benign interaction of the three.Conclusion (1) The experiment using radionuclide scan of gastrointestinal emptying in experimental reflect the objective of the Rat gastrointestinal motility index, showed by STZ Model of diabetic rats do exist gastrointestinal motility weakening phenomena, prompting DGP model induced by successful; EA group compared with the model group, gastric emptying was significantly enhanced and more effective than western medicine group, gastrointestinal propulsion rate was significantly higher, indicating that EA has a strong role in improving the gastrointestinal motility; In addition, electro-acupuncture group after treatment, blood glucose levels were lower than the model group, it shows that acupuncture is not only a strong role in promoting gastrointestinal motility, but also may adjust the blood glucose of DGP rats by accelerating gastric emptying.(2) Electro-Acupuncture can reduce MTL and GAS content of DGP rat in peripheral blood while increase SS; at the same time, it can accelerate gastric emptying function and regulate the DGP rat Gastric motility function by raising MTL and GAS content of DGP rat in gastric antrum tissue while reducing the content of SS. The gastrointestinal hormones changes in antral tissue seem to be more directly reflect the status of its gastrointestinal function.(3) After gastrointestinal injury, morphological ultrastructure of Cajal interstitial cell in gastric antrum has been changed, organelles reduced, especially to reduce the number of mitochondrial, swelling, dissolved, resulting in the conduction of nerve function to reduce cell excitability; in addition, the gap junctions between neuronal cells and smooth muscle cells drop sharply, and control of muscle cell motility in the intermediary function decreased significantly, resulting in slow-wave rhythm slows down or gastrointestinal disorders; electro—acupuncture intervention intervention ICC Stromal Cells activation and inhibition of ICC excessive proliferation of mesenchymal cells, enhance the ICC cells on the signals received and stability of gap junction and maintain the balance of gastrointestinal hormone of MTL and GAS, SS content, so as to promote the ICC interstitial cell and gastrointestinal hormones in benign interaction; and the reaction of gastrointestinal neural networks so as to promote the restoration of the ICC structure, improving the structure of intercellular gap junctions, affecting the transfer function of gastric—electric rhythm, to achieve the goal of promoting the reconstruction of gastric motility. (4) After gastrointestinal dysfunction in DGP rats, there are closely relation among changes of gastrointestinal emptying, gastrointestinal hormones of MTL, GAS, SS and ICC content in rats, electro-acupuncture may be passed ICC Stromal Cells activation, promoting the benign interaction of the ICC cells function and gastrointestinal hormone, thus affecting morphology remodeling of the cells of gastric antrum and delivery, to achieve the goal of promoting gastrointestinal reconstruction.(5) In light of the results of the study, we think that the quality of the acupuncture starting neural-network control and promoting gastrointestinal reconstruction play a key role in treating diabetic gastroparesis.