| Diabetic gastroparesis(DGP)is one of the common chronic complications of diabetes under the combined influence of complex multi-factors.It can usually cause severe fluctuations in blood glucose,dehydration and malnutrition in people with diabetes.Due to the slow progress of DGP,the symptoms are mostly insidious and often misdiagnosed or ignored.At present,the pathogenesis of DGP is not clear yet,and Western Medicine treatment is mostly symptomatic.Study on the pathogenesis and specific treatment methods of DGP is still the main direction of the current research.With the development of neurogastroenterology and neuroendocrinology,the role of neuroendocrine mediated by various brain-intestinal peptides and neurotransmitters in the pathogenesis of DGP is getting more and more attention.DGP is categorized to Traditional Chinese Medicine diseases such as "consumptive thirst" and "distention and fullness".Its onset is due to the long course of diabetes,which consumes Qi and Yin;or the poor feelings,Liver qi invading spleen and stomach,or the food stagnation;or the blood stasis,or the poor function of spleen and stomach in receving food and drink caused by the weakness of spleen and stomach.The thesis is based on the "Foxiang san"created by the Chinese medicine master Renhe Lv,which has the functions of regulating Qi and strengthening the spleen,dispelling phlegm and directing Qi downward to relieve vomitting,discuss the efficacy,potential mechanism and target of Foxiang san in the treatment of diabetic gastroparesis from the perspective of endocrine regulation.The thesis includes literature review,clinical research and animal experiments.Objective:To observe the effect of Foxiang san on glucose and lipid metabolism and dopamine in DGP patients through clinical research,to analyze the efficacy of Foxiang san in treating DGP patients with spleen deficiency and Qi stagnation,and to explore its target spontaneously,further through animal experiment to observe the effects of Foxiang san in regulating blood glucose metabolism indexes,gastric motility indexes such as motilin and small intestine propulsion rate in diabetic gastroparesis rat model,peripheral blood dopamine,brain tissue striatum dopam:ine D2 receptor and related organ pathological morphological changes.To indicate Foxiang san's part neuroendocrine mechanism mediated by central and peripheral dopamine targets in the treatment of DGP.Methods:In the clinical research part of this subject,patients with a clear diagnosis of DGP were randomly divided into Western medicine group(WMG)and Traditional Chinese medicine group(TCMG).On the basis of good-controlled glucose level(fasting blood glucose is maintained at 6.0-8.0 mmol/L,blood glucose is maintained at 8.0-10.0 mmol/L 2 hours after a meal,glycated hemoglobin<7.0%)result from health education,diet control,appropriate exercise,oral hypoglycemic drugs or insulin injections,domperidone 10mg/time was taken 30 minutes before meal 3 times per day in WMG;Foxiang san(main ingredients:bergamot,citron,incense,etc.)is taken in 30 minutes before meal,200 ml each time and 2 times per day in TCMG.The course of treatment in both groups is 4 weeks.Observing the the changes of blood glucose,low-density lipoprotein,triglyceride,total cholesterol,peripheral blood dopamine,scales of spleen deficiency and qi stagnation,TCM symptom efficacy,gastroparesis main symptom index scale score,barium strips before and after the therapy.In the animal experiment part of this study,STZ was injected to SD rats intraperitoneally to establish the diabetic rat model,which is the base of diabetic gastroparesis rat model.After successful modeling,the rats were randomly divided into 5 groups,respectively,as the model group(MG),Western medicine group(WMG,)and Foxiang san high,medium and low dose groups(FHG,FMG,FLG),and compared with normal SD rats(Normal group),hematoxylin-eosin staining method was used to observe the changes of gastric and brain tissues in each group of rats.The blood glucose was detected by an automatic biochemical analyzer,the levels of dopamine and motilin in the peripheral blood of each group of rats were measured by the enzyme-linked immunosorbent assay(ELISA)method,and the dopamine D2 receptors of the striatum of each group of rats were detected by immunohistochemical SABC method.All experimental data were statistically processed with SPSS2 1.0 software.Results:1.In clinical research,low-density lipoprotein,total cholesterol,triglycerides in DGP patients could be decreased to varying degrees,and barium emptying rate increased after treatment in the traditional Chinese medicine group,spleen deficiency Qi stagnation syndrome scores,gastroparesis main symptom scale score and peripheral blood dopamine level 'were lower(P<0.05),compared with before treatment;the TCM syndrome score was reduced(P<0.05),the rate of syndrome score' was significantly increased,and the peripheral blood dopamine level was reduced(P<0.05).The effective rate of symptoms such as "loss of appetite","fatigue","chest tightnes","frequent sighing","sleepy","stool loosening" was significantly increased,the difference was statistically significant(P<0.05);age,spleen deficiency and qi stagnation scores were significantly positive related to GCSI score before treatment(r>0,P<0.05),and there was a significant negative correlation between the triglycerides and barium emptying rate and the GCSI score before treatment(r<05 P<0.05),further multiple linear regression analysis showed that the lower barium emptying rate accompany with higher the fullness score and GCSI score.The overall effective rate in the Chinese medicine group was 61.29%,and the overall effective rate in the western medicine group was 66.67%.There was no statistically significant difference in the overall effective rate between the two groups(P>0.05).In the traditional Chinese medicine groups,there were statistically significant differences in the DM course,history of dyslipidemia,barium emptying rate,and DA between the effective and ineffective groups(P<0.05),and the DM course,history of dyslipidemia,the ratio and DA level in the ineffective group were significantly higher than the effective group,and barium emptying rate in the ineffective group was significantly lower than that in the effective group(P<0.05).There was a significant positive correlation between DM course and DA and the ineffectiveness(P<0.05),and they were independent risk factors(OR>1)that affects the ineffectiveness of the Chinese medicine group,namely,the greater the DM course and the higher the DA value are,the higher the probability of the patient's ineffectiveness is.After analyzing the predictive indexes of curative effect,it was found that DA level(corresponding diagnostic cut-off point was 86.3431)and DM disease course(corresponding diagnostic cut-off point was 10.5)both indexes had good predictive effect on curative effect,and the combined detection and predictive effect of the two indexes was better than DA,DM disease course two separate predictions.2.Animal experiments found that the blood glucose of the blank group was significantly lower than that of the western medicine group,model group and traditional Chinese medicine group(P<0.05);compared with the blank group,the small bowel advancement rate of the MG,FHG and FLG was reduced;Compared with the model group,the FMG and the WMG had a higher intestinal propulsion rate(P<0.05);compared with the normal group,the motilin in the MG decreased significantly.Compared with the MG,the motilin level in the WMG and the traditional Chinese medicine groups especially the FMG was significantly increased.Compared with the normal group,the number of neurons in the intermuscular plexus of the gastric tissue in the MG was also decreased,longitudinal muscles became significantly thinner,gastric mucosal epithelial cells became thinner and missing,cell spaces became larger,vacuoles were formed in the cytoplasm,and capillaries were visible under the light microscope.After treatment with Chinese medicine,the number of neurons in the gastric intermuscular plexus in the FMG Increased,circular muscles and longitudinal muscles thickened,intercellular widening,no cytoplasm formation,and no capillary dilation,compared with the normal group,the number of hippocampal neurons in the model group was reduced,and the cell matrix was looser.There is in the pulp Follicles,glial cells surrounding small blood vessels,thickened blood vessel walls,lightly stained neuronal cytoplasm,widened blood vessel gap,neurons decreased slightly,hippocampal neurons stained closely by Nissl body staining,cortical area The neuron cytoplasm was dark blue in rats treated with traditional Chinese medicine.After treatment with traditional Chinese medicine,the mentioned brain pathological changes were improved,compared with the normacl group,the DA levels of the MG increased,compared with the MG,the DA level of the traditional Chinese medicine groups was somewhat decreased(P<0.05);compared with the MG,the mean optical density of DA2R in rats of the normal group and each dose group of traditional Chinese medicine increased significantly(P<0.05),of which the most significant increase in FMG(P<0.05).Conclusion:Traditional Chinese Medicine(TCM)Foxiang san can improve the glucose and lipid metabolism disorder in DGP patients to some extent,and decrease the peripheral blood DA level in patients with diabetic gastroparesis,increase the gastric emptying rate,reduce the GCSI score,alleviate the symptoms of delayed gastric emptying,and reduce the symptoms of spleen deficiency qi stagnation syndrome scores and improve TCM symptoms significantly better than the Western medicine group.Therefore,Foxiang san has a certain effect on the prevention and treatment of delayed gastric emptying in DGP patients with spleen deficiency and Qi stagnation syndrome;The DA level may be the targets of Foxiang san in the treatment of diabetic gastroparesis.DGP rats established on the basis of diabetic rats may have a significant decrease in rat small intestine propulsion rate,and obvious lesions in gastric tissues observed under light microscope,Foxiang san may reduce DA by activating striatum DA2R Motilin level,then promote the small bowel advancement rate,improve the gastric emptying fucntion and glucose disorder of DGP,delay the pathological damage of the stomach and brain of DGP rats,and has certain preventive effects on diabetic stomach and brain complications. |
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