| ObjectiveTo comparing the Traditional Chinese Medicine(TCM)syndromes of patients with type 2 diabetes(in line with phlegm and blood stasis syndrome)before and after treating by Shuzheng Granule,to explore the Dialectical main points of Shuzheng Granule on treating type 2 diabetes.And as the PI3K/AKT signal pathway is closely related to the developmnet of Type 2 diabetes,so we put the signal pathway in this experimental study as the BreAKThrough point,to explore the molecular mechanism of Shuzheng Granule on treating type 2 diabetes.Methods1.A prospective,single-blind,controlled study was included in 72 cases of type 2 diabetes mellitus with phlegm and blood stasis syndrome and were randomly divided into control group and Shuzheng Granule group,the control group were given basic treatment of type 2 diabetes,including antihyper--tensive,hypoglycemic,Lipid reduction.etc.Patients in another group received the same basic treatment and Shuzheng granules.the mean follow up was 12 weeks.The two groups of patients were collected in detail,such as sex,age,duration of diabetes,combined disease and other basic information before and after treatment FPG,HbA1 c,TCM syndromes and other points,compared the control group and Shuzheng Granule group and Shuzheng Granule before and after itself comparison,using the appropriate statistical methods,To explore the dialectical points Shu Shu particles treatment of type 2 diabetes mellitus phlegm and blood stasis.2.70 female Sprague-Dawley rats were assigned to a normal group(n=10)and an experimental group(n=60,considering the Probability of death and failure during making the model of type 2 diabetes),All rats in experimental group were injected STZ(25-35mg/kg)in abdominal cavity one-time making the FPG?16.7mmo/L,and then feding with fatty emulsion in six weeks.After 6 weeks,50 rats were randomly divided into 5 groups: model group,metformin group,Shuzheng granules high,medium and low dose group,10 rats in each group,Same fatty emulsion and different dose groups of Shuzheng Granule(540mg?270mg?135mg/100g?d)or metformin(180mg/100g?d)were administrated by gavage to the 5 groups diabetic rats for 4 weeks.After 4 weeks of treatment,blood samples were taken to determine fasting blood glucose(FPG),glycosylated hemoglobin(HbA1c),and fasting insulin(FINS).Liver tissue for western-bloting and RT-PCR to measure the protein and mRNA level of Insulin Receptor Substrate(IRS-2)?phosphoinositide3-kinase(PI3K)?proteinkinase B(AKT2)?Glycogen synthase kinase-3?(GSK3?)?Forkhead transcription factor-1,(FOXO1)?Phosphoenolpyruvate carboxykinase(PEPCK)?glucose-6-Phosphatase,(G6P)?Glucose Transporter-4(GLUT4)?phosphatase and tensin homolog deleted on chromosome ten(PTEN)on the PI3K/AKT signal pathway.Results1.Clinical observation:Shuzheng Granule can significantly reduce FPG and HbA1 c in type 2 diabetic patients,which were significantly different from those in control group(P<0.01 or 0.05),and were significantly different from those before treatment(P<0.01).Shuzheng Granule can obviously ameliorate the Chinese medicine symptoms of diabetic patients,the efficient rate at all was 88.89%,Compared with the control group,the rate was obviously different(P<0.05).Compared to control group and before treatment,the syndrome scores of TCM were obviously reduced treating by Shu Zheng Granule(P<0.01).Patients in the Shuzheng granule group were thirsty before treatment and after treatment.They had a lot of thirst,pale mouth,sputum and phlegm,nausea,vomiting,difficulty in suffocation,dizziness,tiredness,fatigue,shortness of breath,laziness,dull complexion,impatience,blurred vision.There was a significant difference in the frequency of clinical syndromes of numbness,limb numbness,lower extremity pain,chest tightness,chest pain,and urine yellowness(P<0.01).Thirsty do not want to drink,mouth dry mouth,abdominal distention,tinnitus,body fat,diarrhea(P<0.05).There was no significant difference in the frequency of clinical syndromes such as susceptibility to hunger,food,headache,insomnia,palpitations,fear of heat,sweating,edema,constipation,frequent urination,and pale tongue blemishes,and greasy tongues(P>0.05).Compared with before treatment,after treatment,Shu Zheng granules showed pale mouth,phlegm,mouth dry mouth,abdominal distention,nausea,vomiting,headache,dizziness,tiredness,fatigue,shortness of breath,dizziness,darkness,and impatience.Insomnia,blurred vision,limb numbness,pain in the lower extremities,chest tightness,chest pain,pale teeth with numbness,and median scores of the TSS were significantly different(P<0.01).The thirst for thirst,drink,thirst,desire to drink,diet decreased,and the median urine syndrome score was significantly different(P<0.05).There was no significant difference in the median of multiple syndrome scores of hunger,food,headache,palpitation,tinnitus,heat-hyperhidrosis,edema,body fatness,diarrhea,constipation,and urinary frequency(P>0.05).2.Experiment: Compared with the model group,FPG,HbA1 c,and FINS were significantly decreased in the high,middle,and low doses of Shuzheng Granule and metformin group(P<0.05).Compared with metformin group,there was no difference in high dose group of Shuzheng Granule(P>0.05).Compared with the model group,the protein content and mRNA expression of IRS-2,PI3 K and AKT2 in high dose group increased,with statistical difference(P<0.01 or P<0.05),the protein content and mRNA expression of GSK3?,FOXO1,PEPCK,G6 P and PTEN decreased with statistical significance(P<0.01 or P<0.05).The AKT2 mRNA expression was increased and the expressions of GSK3?,FOXO1 and PEPCK mRNA were lower in medium and low dose groups(P<0.01 or P<0.05),IRS-2,PI3 K mRNA expression increased,G6 P,PTEN mRNA expression decreased,but no significant difference(P>0.05).The protein content of IRS2 and AKT2 inmedium dose group of Chinese medicine increased,while the contents of PEPCK,G6 P and PTEN decreased(P<0.01 or P<0.05),the content of PI3 K protein increased,GSK3 ?,FOXO1 protein content decreased,but the difference was not significant(P>0.05);the content of AKT2 protein in the low dose group of traditional Chinese medicine increased,the content of PEPCK,G6 P and PTEN decreased,with statistical significance(P<0.01 or P<0.05),PI3 K,IRS2 protein content,GSK3?,FOXO1 protein content decreased,but the difference was not significant(P>0.05).The contents and mRNA expressions of GLUT4 in high,medium and low dose groups of Shu Zheng Granule all increased,statistical difference was not existed(P>0.05).ConclusionClinical observation: Shuzheng granules can significantly reduce FPG and HbA1 c levels in patients with type 2 diabetes mellitus and improve patients with diabetes-related syndromes,including light mouth,sticky mouth,nausea,vomiting,weight loss,dizziness,tiredness,shortness of breath,lazy expression,complexion Obscure darkness,upset irritability,blurred vision,limb numbness,pain in the lower extremities,chest tightness,and chest pain can improve the symptoms.In the clinical application of Shu Zheng granules in the treatment of diabetes,the 14 major syndromes mentioned above can be used as dialectical points for the use of Shu Zheng granules.2.Experiment: Shuzheng Granule can increase the activity of PI3K/AKT signaling pathway-related molecules in liver of STZ model + high fat diet diabetic rats,may be achieved through the following ways:(1)Improve the activity of IRS/PI3K/AKT protein,inhibit the expression of GSK3?,thereby enhancing the activity of glycogen synthase,promoting glycogen synthesis and lowering blood glucose.(2)Improve PI3K/AKT activity,inhibit the expression of FOXO1,thereby reducing the activity of gluconeogenic genes G6 P and PEPCK,reducing gluconeogenesis.(3)Downregulate the expression of PTEN,a negative regulator of PI3K/AKT,thereby reducing its inhibitory effect on PI3K/AKT signaling pathway and making this pathway play a normal role in enhancing insulin sensitivity and reducing insulin resistance. |
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