| This study consists of two parts:the intervention effect of traditional Chinese medicine on spleen-kidney qi deficiency syndrome of type 2 diabetes mellitus and the mechanism of Shenqi Jiangtang granule on diabetic rats1 Clinical StudyObjective:To explore the clinical characteristics of the syndrome of spleen-kidney Qi deficiency in diabetes patients and observe the clinical efficacy of traditional Chinese medicine in treating type 2 diabetes patients with spleen-kidney Qi deficiency syndrome,and analyze the relevant factors affecting the treatment effect.Methods:A self-controlled before-and-after study was conducted.General information,TCM syndrome,quality of life,physical and chemical indicators and other related data of type 2 diabetes patients with spleen-kidney Qi deficiency syndrome who were treated in the Endocrinology Department of Guang’anmen Hospital from January 2022 to January 2023 were collected to establish a database.The clinical characteristics of spleen-kidney Qi deficiency syndrome,such as TCM demographic characteristics,course of disease,concurrent diseases,and clinical symptoms were explored.Blood glucose,blood lipids,glycated hemoglobin,TCM syndrome score,and quality of life score were recorded before and after Chinese medicine treatment.After the observation was completed,the data were collated,statistically analyzed,and the clinical efficacy was evaluated,and the relevant factors affecting the treatment effect were analyzed.Results:This study included 100 patients with type 2 diabetes and spleen-kidney Qi deficiency syndrome.The study found:(1)Clinical characteristics:① Gender distribution:Among 100 patients,there were 47 males and 63 females,with a ratio close to 1:1;② Characteristics of age and disease course distribution:The patients included in this study were mainly middle-aged and elderly,and the proportion of the elderly group was the highest,reaching 51%,and the proportion of patients with a disease course of more than 10 years was the highest,reaching 39%.③Concurrent diseases and complications:98%of patients had other diseases,among which the most common was hyperlipidemia,accounting for 79%.Diabetes complications mainly included peripheral neuropathy,diabetic nephropathy,diabetic retinopathy,diabetic peripheral vascular disease,and diabetic gastroparesis.Among them,the proportion of patients with peripheral neuropathy was the highest,accounting for 21%.(2)Therapeutic efficacy observation:① Blood glucose:After 12 weeks of Chinese herbal intervention,the level of glycated hemoglobin in patients was significantly reduced.Fasting blood glucose and postprandial 2-hour blood glucose both showed significant decreases after 4,8,and 12 weeks of treatment with Chinese herbal medicine compared to before treatment.② Blood lipids:After Chinese herbal treatment,TC,TG,and LDL-C all showed significant decreases.③ Physical signs:BMI and systolic blood pressure both showed significant decreases after 4,8,and 12 weeks of treatment with Chinese herbal medicine compared to before treatment,while diastolic blood pressure showed a decrease after 4 and 12 weeks of treatment.④TCM syndrome score:After Chinese herbal intervention,the TCM syndrome score showed a significant decrease with statistical differences.⑤ Quality of life score:The quality of life score showed a significant decrease after 4,8,and 12 weeks of treatment with Chinese herbal medicine compared to before treatment,with statistical significance.⑥Medication use:Shenqi Jiangtang Granules were the most commonly used Chinese patent medicine for treating diabetes.The frequency of use for initial,second,third,and fourth visits were 30,40,49,and 48,respectively.Modified Shenqi Dihuang Decoction was the most commonly used Chinese herbal formula,with the frequency of use for initial,second,third,and fourth visits being 14,18,21,and 50,respectively.After Chinese herbal intervention,the number of hypoglycemic drugs and concurrent medications used decreased significantly,with statistical significance.⑦ Safety evaluation:No significant safety issues were found during the study process.Patients’ vital signs,blood routine,urine routine,liver function,renal function,and electrocardiogram were stable before and after treatment,with no significant abnormal changes.No significant adverse reactions such as nausea,vomiting,diarrhea,or allergies were observed.(3)Therapeutic efficacy influencing factors:① Correlation analysis:Systolic blood pressure,BMI,heart rate,triglycerides,blood urea nitrogen,TCM syndrome score,and quality of life score were positively correlated with glycated hemoglobin after treatment,while total bilirubin was negatively correlated.Systolic blood pressure,heart rate,serum urea nitrogen,glycated hemoglobin,and quality of life score were significantly positively correlated with TCM syndrome score after treatment.Smoking history,serum urea nitrogen,glycated hemoglobin,and TCM syndrome score were positively correlated with quality of life score after treatment.② Regression analysis:BMI was an independent risk factor for unqualified glycated hemoglobin(OR=0.804,95%CI interval 0.6470.998,P=0.048).Baseline glycated hemoglobin was an independent risk factor for unqualified glycated hemoglobin after treatment(OR=0.321,95%CI interval 0.1710.601,P=0.000).Linear regression found that baseline glycated hemoglobin and TCM syndrome score had a statistically significant impact on TCM syndrome score after treatment,with regression coefficients of 0.368 and 0.185,respectively.Baseline TCM syndrome score and quality of life score had a statistically significant impact on quality of life score after treatment,with regression coefficients of 0.352 and 0.287,respectively.Conclusion:(1)Clinical features:type 2 diabetes mellitus with deficiency of spleen,kidney,and qi evidence mostly occurs in elderly people over 60 years of age,and the duration of the disease is mostly greater than 10 years.patients with T2DM with deficiency of spleen,kidney,and qi evidence mostly combine with other diseases,and hyperlipidemia is the most common combined disease.The main symptoms of TCM are tiredness and weakness,and the secondary symptoms are spontaneous sweating.(2)Therapeutic effect:Chinese medicine treatment for type 2 diabetes mellitus patients with deficiency of spleen and kidney qi has the effect of controlling blood glucose,improving dyslipidemia and reducing body weight,which can help reduce the dosage of western medicine,significantly improve clinical symptoms,improve survival quality and have good safety.(3)Efficacy influencing factors:BMI and baseline glycosylated hemoglobin risk factors affecting glycosylated hemoglobin status after TCM treatment,baseline glycosylated hemoglobin is a risk factor affecting TCM evidence score after TCM treatment,and baseline TCM evidence score is a risk factor affecting survival quality score after TCM treatment.2 Experimental studyOBJECTIVE:To investigate the mechanism study of ginseng and astragalus hypoglycemic granules to protect pancreatic β-cells in type 2 diabetic rats by regulating Ferroptosis,and to provide a reference basis for exploring new ideas for the treatment of T2DM.METHODS:Male SD rats were selected and a type 2 diabetes model was established by high-fat diet plus STZ.The rats were gavaged with Ginseng and Glucose-lowering pellets for 8 weeks,and observed and examined(1)general conditions:mental status,coat color,activity,survival status and body weight of each group;(2)blood glucose related indexes:determination of fasting blood glucose(FPG),glucose tolerance test(OGTT)and fasting insulin(FINS);(3)pancreatic morphology:observation of pancreatic islet morphology under HE staining light microscopy and ultrastructure of pancreatic islet cells by transmission electron microscopy;(4)pancreatic tissues in the pancreatic tissue.④ Redox levels in pancreatic tissues:detection of SOD,H2O2,CAT,GSH-PX,GSH,MDA levels in rat pancreatic tissues;⑤Iron load detection:detection of ferritin levels in pancreatic tissues;⑥Ferroptosis-related gene mRNA and pathway proteins:WesternBlot detection of Ferroptosis pathway-related pathway ACSL4,GPX4 protein expression in rat pancreatic tissues,GPX4 protein expression in rat pancreatic tissue by WesternBlot,and mRNA levels of ACSL4 and GPX4 in rat pancreatic tissue by qRT-PCR.Results:(1)Body weight:ginseng-stragalus hypoglycemic granules could improve the body weight of T2DM rats(P<0.05).(2)Blood glucose and insulin:(1)Fasting blood glucose:at 4 weeks of drug intervention,compared with the model group,FBG was not significantly reduced in the low and medium dose groups of Shenqi Jiangtang Granule(P>0.05),and FBG was significantly reduced in the high dose group of Shenqi Jiangtang Granule and metformin group,with statistically significant differences(P<0.01);at 8 weeks of drug intervention,FBG was significantly reduced in each drug intervention group compared with the model group,with statistically significant differences(p<0.01).(ii)Fasting insulin The fasting insulin levels in the middle and high dose groups of ginseng and astragalus hypoglycemic granules and metformin group were significantly elevated compared with the model group,with statistical differences(p<0.01);the mean fasting insulin levels in the low dose group were elevated compared with the model group,but there was no statistical difference(p>0.05).(3)Area under the curve of glucose tolerance glucose:the area under the curve of glucose tolerance glucose:each dose group of Ginseng Qi hypoglycemic granules and metformin group decreased compared with the model group,and the difference was statistically significant(P<0.05)or statistically significant(P<0.01).(3)Histomorphology:① HE staining:vacuolar degeneration and necrotic cells were reduced in the ginseng granules group compared with before,and ginseng granules had a significant protective effect on islet structure,and the high-dose group of ginseng granules was significantly better than the low-dose group.② Transmission electron microscopy:Diabetic rats had reduced cell volume,decreased number and density of secretory granules,damaged mitochondrial structure,blurred or disappeared mitochondrial cristae structure,abnormally increased membrane density,and more obvious features of cellular Ferroptosis.After the intervention of Shenqi Jiangtang Granule,the mitochondrial structure was improved,the cristae structure was more obvious,the density of secretory granules was increased,and the development of Ferroptosis was inhibited,and the high-dose group had a stronger protective effect on cell structure than the low-dose group.(4)Oxidative stress level:Compared with the model group,there was an increasing trend of SOD,CAT,GSH and GSH-PX and a decreasing trend of MDA and H2O2 in the low-dose group of ginseng-stragalus hypoglycemic granules,but there was no statistical difference(P>0.05).In the middle dose group,SOD increased significantly,and the difference was statistically significant(P<0.05).SOD and GSH increased significantly and MDA and H2O2 decreased significantly in the high-dose group of,Shenqi Jiangtang Granule,and the differences were statistically significant(P<0.05)or statistically significant(P<0.01)(5)Iron load:compared with the model group,the ferritin content of pancreatic tissue was significantly reduced in the metformin group and each dose group of ginsenoside,and the difference was statistically significant(P<0.05)or significant(P<0.01).Compared with the metformin group,the ferritin content of pancreatic tissues in all dose groups of ginseng and astragalus hypoglycemic granules decreased,among which the high dose group of ginseng and astragalus hypoglycemic granules significantly decreased,and the difference was statistically significant(P<0.05)Ferroptosis-related mRNA and protein expression levels:① mRNA expression levels of ACSL4 and GPX4:compared with the model group,the mRNA expression levels of ACSL4 in the middle dose group of Ginseng Astragaloside Granules decreased,and the difference was statistically significant(P<0.05);the mRNA levels of ACSL4 and GPX4 in the pancreatic tissue of rats in the high dose group of Ginseng Astragaloside Granules decreased,and the mRNA levels of GPX4 increased significantly,and the difference was statistically significant(P<0.05).The differences were statistically significant(P<0.05)or statistically significant(P<0.01).(2)ACSL4 and GPX4 protein expression levels:compared with rats in the model group,ACSL4 protein expression levels decreased and GPX4 protein expression levels increased significantly in rat pancreatic tissues after metformin intervention,and the differences were statistically significant(P<0.01).(6)Compared with the metformin group,the expression levels of ACSL4 and GPX4 in pancreatic tissues of rats in the high-dose group of,Shenqi Jiangtang Granule decreased and the expression levels of GPX4 increased significantly,and the differences were statistically significant(P<0.05).The results of the study indicated that ginseng and astragalus hypoglycemic granules had the effect of regulating the expression level of Ferroptosis-related proteins.Conclusion:(1)Shenqi Jiangtang Granule can significantly reduce FBG,improve glucose tolerance,reduce the area under the blood glucose curve in glucose tolerance test and increase insulin secretion in T2DM rats.(2)Shenqi Jiangtang Granule can improve the degree of oxidative stress in T2DM rats,enhance the anti-peroxidation ability of pancreatic tissues and reduce the accumulation of peroxides.(3)Shenqi Jiangtang Granule can regulate Ferroptosis,up-regulate the mRNA and protein expression of GPX gene,and down-regulate the expression of ACSL4 to protect βcells from Ferroptosis. |
PDF Full Text Request