RESUMO
Objective:To study the effect of Baihutang on blood glucose， blood lipid metabolism and vascular remodeling in type 2 diabetic rats and its regulation on insulin receptor substrate-1（IRS-1）/ phosphatidylinositol-3 kinase（PI3K）/ protein kinase B（Akt） signal pathway. Method:The 90 rats were randomly divided into normal group， model group， Baihutang low， middle and high dose groups and metformin group， with 15 rats in each group. Except for normal group， the other rats were injected intraperitoneally with streptozotocin to establish the model of type 2 diabetes. The rats in the low， middle and high dose groups were given Baihutang formula granules of 5， 10， 20 g·kg-1 respectively according to their body weight. The positive control group was given metformin （100 mg·kg-1） by intragastric administration， while those in the control group and model group were given the same amount of normal saline once a day for 12 weeks. The levels of fasting blood glucose， glycosylated hemoglobin， serum tumor necrosis factor-α（TNF-α）， interleukin-6（IL-6）， interleukin-1 β（IL-1β）， total cholesterol（TC）， triglyceride（TG） and low-density lipoprotein cholesterol（LDL-C） were measured after administration. The levels of sterol regulatory element binding protein 1C （SREBP1C）， acetyl CoA carboxylase （ACC）， fatty acid synthase gene （FASN） and carnitine palmitoyl transferase 1A （CPT1A）， acylcoa oxidase 1（ACOX1）， recombinant human acylcoa dehydrogenase （ACADM） mRNA in liver of rats were detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， Western blot was used to detect the protein levels of IRS-1， PI3K and Akt in liver of rats. Hematoxylin-eosin（HE） staining was used for histopathological examination of rat thoracic aortic vessels. The migration ability of vascular smooth muscle cells in rat thoracic aorta was detected by scratch test. Result:Compared with the normal group， the fasting blood glucose， glycosylated hemoglobin， serum TNF-α， IL-6，IL-1β， TC，TG and LDL-C levels， liver lipid synthesis gene mRNA level and vascular smooth muscle cell migration ability of thoracic aorta in model group were significantly higher than those in normal group （P<0.05）， while fatty acid oxidation gene mRNA level and IRS-1，PI3K，Akt protein level in liver were significantly decreased in model group （P<0.05）. The vascular wall thickness of thoracic aorta increased significantly in rats （P<0.05）. Compared with model group， the levels of fasting blood glucose， glycosylated hemoglobin， serum TNF-α，IL-6， IL-1β， TC， TG and LDL-C， the level of lipid synthesis gene mRNA in liver and the migration ability of vascular smooth muscle cells in thoracic aorta of rats in all Baihutang groups were significantly lower than those in model group （P<0.05）. The mRNA level of fatty acid oxidation gene and the protein levels of IRS-1， PI3K and Akt in liver were significantly increased（P<0.05）， and the histopathology of thoracic aorta was significantly improved and the vascular wall thickness decreased significantly（P<0.05）. Conclusion:Baihutang can reduce the levels of blood glucose， blood lipid and serum inflammatory factors in type 2 diabetic rats， regulate the expression of genes related to lipid metabolism in liver， and improve the histopathology and vascular remodeling of thoracic aorta. The mechanism may be related to the regulation of IRS-1/PI3K/Akt signal pathway.
RESUMO
Objective To investigate the effects of angelica lactone combined with Xiaoke pill on blood glucose regulation, renal protection and vascular endothelial growth factor signal pathway in diabetic nephropathy rats. Methods Totally 75 rats were randomly divided into control group, model group, Xiaoke pill group, angelica lactone group and angelica lactone combined with Xiaoke pill group, with 15 rats in each group. Except for the control group, the rest of the rats established diabetic nephropathy model. Rats in Xiaoke pill group, angelica lactone group and angelica lactone combined with Xiaoke pill group were given Xiaoke pill (0.8 g/kg), angelica lactone (20 mg/kg), Xiaoke pill (0.8 g/kg) combined with angelica lactone (20 mg/kg), respectively, once for 8 weeks. The levels of 24-hour urinary protein, fasting and postprandial blood glucose, glycosylated serum albumin and glycosylated hemoglobin, fasting insulin and insulin sensitivity index, serum creatinine (SCr) and urea nitrogen (BUN) were measured. The levels of insulin (INS) and glucose-6-phosphatase (G6Pase) mRNA in islet tissue were measured by Real-time PCR. Renal histopathological changes were detected by HE staining. The levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) in rat kidney were detected by Western blotting and immunohistochemistry. Results Compared with the model group, 24-hour urinary protein, fasting and postprandial blood glucose, glycosylated serum albumin and glycosylated hemoglobin, fasting insulin, SCr and BUN, VEGF and VEGFR2 protein levels and relative integral absorbance of kidney tissue in angelica lactone combined with Xiaoke pill group were significantly lower than those in model group(P<0.05). The insulin sensitivity index, the levels of INS and G6Pase mRNA in islet tissue were significantly increased (P < 0.05), and the renal histopathology of diabetic nephropathy rats was significantly improved. Conclusion Angelica lactone combined with Xiaoke pill can reduce blood glucose level, increase insulin sensitivity index, and its mechanism may be related to the regulation of VEGF signal pathway.