| Objective:To study the effects of Dahuang Huanglian Xiexin Decoction on glucose and lipid metabolism,insulin resistance(IR)and PI3K/AKT signaling pathway in type 2 diabetes(T2DM)rats.Methods:(1)A random method was adopted to classify 60 healthy male Wistar rats of SPF grade.Among them,10 normal control group,fed with ordinary feed,Fifty models were made and fed with high-sugar and high-fat feed.(2)After 28 days,all rats were fasted for 12 hours,and the model rats were intraperitoneally injected with streptozotocin(STZ)at a dose of 25 mg/kg.After the injection,the model rats continued to be fed with normal feed for 1 week.After fasting for 12 hours,the fasting blood glucose(FBG)of the rats in each group was measured,and the FBG value ≥7.8mmo1/L indicated that the T2 DM model was successfully established;Rats that have not succeeded in modeling continue to be given intraperitoneal injection of STZ at a dose of 12.5 mg/kg.(3)The model rats were randomly divided into model groups,the low,medium and high dose groups of Dahuang Huanglian Xiexin Decoction and the Jinqi Jiangtang group,with 10 rats in each group.The low,medium,and high doses of Dahuang Huanglian Xiexin Decoction were 6.3 g/kg,12.6 g/kg,25.2 g/kg,respectively.The Jinqi Jiangtang group was administered1.2 g/kg,and the model group and normal The control group was given an equal volume of distilled water.Gavage was administered once a day for 28 days.(4)After the administration,the tail vein blood of the rats was taken,and the rats in each group(FBG)were measured with a blood glucose meter;The rats were anesthetized by intraperitoneal injection of 10% chloral hydrate(0.35 m L/100g)and then sacrificed,and blood was taken from the abdominal aorta.Detect the content of fasting insulin(FINS),total cholesterol(TC),triglycerides(TG)and low-density lipoprotein cholesterol(LDL-C)in serum with Elisa method;The steady-state model insulin resistance index(HOMA-IR)was calculated according to the obtained FBG and FINS.Observe the pathological morphology of the pancreatic tissue of each group of rats with a light microscope,The expression of IRS-1,PI3 K,Akt mRNA in liver tissue was detected by RT-PCR method,Western blot was used to detect the protein expression of IRS-1,PI3 K,and Akt in liver tissues.Result:(1)Compared with the normal control group,rats showed increased diet and water intake,increased urination and defecation,accompanied by the smell of rotten apples,less activity,and lethargy.Slow response,malaise,dull fur and other symptoms,The FBG of the model rats was significantly higher than that of the normal control group(P<0.01),which proved that the model was successful.(2)Compared with the normal control group,FBG,FINS and HOMA-IR in the model group were significantly increased(P<0.01),Compared with the model group,FBG,FINS and HOMA-IR in the low,medium and high dose groups of Dahuang Huanglian Xiexin Decoction decreased significantly(P<0.01);Compared with the normal group,TC,TG,LDL-C in the model group were significantly increased(P<0.01),Compared with the model group,the TC,TG and LDL-C of the low,medium and high dose groups of Dahuang Huanglian Xiexin Decoction decreased significantly(P<0.01).(3)Observe the rat pancreatic tissue under a light microscope.Compared with the normal control group,Part of the pancreatic islet β cells are diffuse,and the pancreatic islet tissue in the pancreas is reduced,Uneven distribution,degeneration of endocrine cells such as pancreatic β cells in some pancreatic islet tissues;Compared with the model group,the islet structure in the pancreatic tissue of the rats in each dose group of Dahuang Huanglian Xiexin Decoction is relatively complete,Pancreatic β-cells increased,pancreatic β-cells showed only slight deformation,and the number of vacuolar cells showed a significant downward trend.(4)Compared with the normal control group,the expression of IRS-1,PI3 K and Akt mRNA in the liver tissue of the model group was significantly decreased(P<0.01),Compared with the model group,the expression of IRS-1,PI3 K and Akt mRNA in the low-dose group of Dahuang Huanglian Xiexin Decoction increased(P<0.01 or P<0.05),The expression of IRS-1,PI3 K and Akt mRNA in the middle and high dose groups of Dahuang Huanglian Xiexin Decoction increased significantly(P<0.01);(5)Compared with the normal control group,the protein expression of IRS-1,PI3 K and Akt in the liver tissue of the model group was significantly decreased(P<0.01),Compared with the model group,the protein expression of IRS-1,PI3 K and Akt in each dose group of Dahuang Huanglian Xiexin Decoction increased significantly(P<0.01).Conclusions:(1)Dahuang Huanglian Xiexin Decoction can reduce blood sugar and blood lipids in T2 DM rats,regulate glucose and lipid metabolism,increase insulin sensitivity,and improve IR.(2)Dahuang Huanglian Xiexin Decoction can improve the histopathological structure of the pancreas,increase the islet β cells,and improve the structure of the islets.(3)Dahuang Huanglian Xiexin Decoction can increase the expression of IRS-1,PI3 K,Akt mRNA and protein and improve IR,which confirms that the effect of Rhubarb Huanglian Xiexin Decoction on improving IR is related to the PI3K/Akt signaling pathway. |
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