作者机构:
[陈学麟] Hunan University of Chinese Medicine, Changsha, 410208, China;[胡剑卓; 陶灵霞] The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410006, China
通讯机构:
[Hu, J.-Z.] T;The Second Affiliated Hospital of Hunan University of Chinese MedicineChina
摘要:
Objective To explore the possible mechanism of Xiaoke Formula (消渴方) for type 2 diabetes mellitus ( T2DM). Methods High-fat and high-sugar feed combined with intraperitoneal injection of 35 mg /kg 2% streptozotocin-citrate buffer were used to establish the T2DM rat model. Forty successfully modeled rats were randomly divided into model group,inhibitor group,Xiaoke Formula group,Xiaoke Formula plus inhibitor group ( combination group),with 10 rats in each group; and another 10 SD rats were set as the normal group. After modeling,rats in the Xiaoke Formula group were given 17 g /( kg·d) Xiaoke Formula by gavage; the inhibitor group was given tail vein injection of 0.5 mg /( kg·d) VIVIT peptide; the combination group received both Xiaoke Formula and VIVIT with the same dose and administration way as other groups; the model group and the normal group were administered with 1.9 ml normal saline by gavage. Five weeks later,levels of fasting blood glucose ( FBG),fasting insulin ( FINS),glycosylated serum protein ( GSP),calcium ion ( Ca~(2+) ) and calcineurin ( CaN) in the pancreatic tissue were detected; HE staining was used to observe the pathological changes of pancreatic islets; the protein expression of insulin and nuclear factor of activated T cell c1 ( NFATc1) in the pancreatic tissue,as well as the mRNA expression of neurogenin 3 ( Ngn3) and pancreaticoduodenal homeobox factor 1 ( PDX-1) were detected. Results Compared to those of the normal group,the FBG and GSP levels of the model group significantly increased,and the expressions of FINS,CaN, Ca~(2+),NFATc1,Ngn3 mRNA and PDX-1 mRNA were all decreased ( P < 0.01). HE staining showed that the cells number of the pancreatic islets was significantly reduced,the shape was irregular,and the interstitium increased; certain islet tissue structures was even completely shrinked and disintegrated. Compared to the model group,Xiaoke Formula group showed better effects on all the outcome measurements ( P < 0.01). HE staining showed that the number of islets increased significantly,and were distributed in complete clumps with richer cytoplasm. Compared to the Xiaoke Formula group,the combination group had increased levels of FBG and GSP,and decreased expression of FINS,CaN,Ca~(2+),NFATc1,Ngn3 mRNA,and PDX-1 mRNA ( P < 0.05 or P < 0.01). Conclusion Xiaoke Formula can regulate blood sugar and protect pancreatic β-cells,the mechanism of which may be related to the regulation of the Ca~(2+) /CaN/NFAT signaling pathway in pancreatic tissue and the increase of β-cell regeneration-related transcription factors.