| Objective:In recent years,the prevalence of Diabetes Mellitus?DM?has increased year by year,especially its complications are a serious threat to human health.DM basic pathological changes in pancreatic ?-cell function is impaired or lost,leading to inadequate insulin secretion.At present,DM's treatment methods include all kinds of hypoglycemic drugs or insulin replacement therapy,but these treatments can only temporarily reduce blood sugar and delay the occurrence of complications,long-term treatment is poor,and long-term medication is also prone to many side effects,Can not fundamentally treat diabetes.In recent years,pancreatic islets or pancreatic transplantation technology has made significant progress,but there are still insufficient donor,rejection and many other bottlenecks,clinical difficult to promote.The traditional Chinese medicine based on its side effects,high safety advantages,in the treatment of DM with significant results.Therefore,the use of traditional Chinese medicine to promote DM status of islet ? cell regeneration,to maintain its insulin secretion function is most likely to fundamentally treatment of DM.In this paper,the effects of total flavonoids of guava leaves on the pancreatic tissue of pancreatic tissue induced by streptozotocin?STZ?were studied.Pancreas-duodenumhomeobox-1,?PDX-1?,neurogenin 3?Ngn3?,NK6 Transcri Ption Factor Associated Locus 1?Nkx6.1?,SRY-related HMG-Box9?SOX9?and Paired box 4?PAX4?,and to explore the mechanism of total flavonoids of guava leaf papaya to promote the regeneration mechanism of islet ? cells in DM state,and to provide new ideas and methods for the treatment of DM.Methods?Several healthy male BALB / c mice weighing about 19 g were injected with STZ for 5 days at a dose of 60 mg · kg-1,and blood collected from the tail vein was measured the fasting blood glucose level once every week until the fasting blood glucose of the mice was 11.1 mmol · L-1.Then the frequency became every 3days.The fasting blood glucose concentration was?11.1 mmol · L-1 was the success of the diabetic mouse model,and the mean blood glucose was taken by 3 times as the blood glucose of the diabetic model mice before treatment.The mice whose fasting blood glucose concentration was11.1 mmol · L-1 were discarded at 8 weeks.The STZ diabetic mice were random Ly divided into model group?n = 10?,the total flavonoids of guava leaves low dose group?n=10?,the guava leaf flavonoids high dose group and the metformin group?n = 10?,and 10 health control mice.The total flavonoids of guava leaves were dissolved in distilled water,and the dosage of the extract was 2g ·kg-1,1g · kg-1,that is,the total flavonoids of guava leaves was 0.396 g · Kg-1 · d-1,0.198 g · kg-1 · d-1,metformin was administered at 0.0875 g · kg-1 · d-1,normal and STZ-diabetic model groups were given equal volume of distilled water.After 2 weeks,the fasting blood glucose,body weight and HE staining were used to observe the Pathological changes of pancreatic islets.RT-PCR,Western blot and IHC were used to detect pancreatic islet ? the expression of PDX-1,Ngn3,Nkx6.1,SOX9,PAX4 m RNA and protein were analyzed.Results : This study showed that fasting glucose in STZ-induced DM mice was significantly higher than that in normal mice?P<0.01?,and the body weight was lower than that in normal mice?P <0.05?.Compared with STZ-induced DM mice,the body weight in the total flavonoids of guava leaf and the metformin group was increased?P<0.05?,and the fasting blood glucose was decreased obvious?P<0.05?.HE staining showed that the islets of the model group were severely damaged and scattered.The total flavonoids and metformin group of guava leaves were less destructive than the model group,and the number and volume of islets increased,the islets were flaky or along the distribution of pancreatic ducts.IHC showed that the expression of PDX-1 in pancreatic tissue of DM group was significantly lower than that of normal group?P<0.05?.The expression of PDX-1 in the total flavonoid treatment group and metformin treatment group were significantly higher than those in DM group in pancreatic tissue of mice.Real-time PCR and Western blot showed that the expression of PDX-1,Ngn3,Nkx6.1,SOX9,PAX4 m RNA and the protein in pancreatic tissue of DM model group were significantly higher than those in control group?P<0.01?.Compared with the DM model group,the expression of PDX-1,Ngn3,Nkx6.1,SOX9,PAX4 m RNA and the protein in pancreatic tissue of the total flavonoids and metformin treatment group were significantly higher?P <0.05?,and correlated with the dose of total flavonoids of guava leaves.Conclusions?1,In DM model mice,the islet cells were severely damaged,fasting blood glucose levels were significantly increased,pancreas tissue islet regeneration related to the expression of transcription factors decreased significantly.2,the total flavonoids of guava leaves can significantly reduce the blood glucose level,slow down the destruction of islet cells,and upregulate the expression level of islet regeneration in pancreatic tissue of DM mice.3,the total flavonoids of guava leaves have a protective effect on islets of DM mice,and the mechanism may be related to the up-regulation of the expression of transcription factors related to the regulation of islet ?-cell regeneration. |
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