Effects of Zuogui Jiangtang Tongmai Recipe on necroptosis pathway in a rat model of type 2 diabetes mellitus complicated with cerebral infarction
10.3969/j.issn.1001-1528.2024.09.014
- VernacularTitle:左归降糖通脉方对2型糖尿病合并脑梗死大鼠坏死性凋亡通路的影响
- Author:
Yu-Zhe CAI
1
;
Ding-Xiang LI
;
Yi-Xuan LIU
;
Zheng LUO
;
Jing-Jing YANG
;
Han-Lin LEI
;
Ya-Nan ZHANG
;
Qin WU
;
Jing CHEN
;
Yi-Hui DENG
Author Information
1. 湖南中医药大学中西医结合学院,湖南 长沙 410208;湖南中医药大学中西医结合心脑疾病防治湖南省重点实验室,湖南 长沙 410208
- Keywords:
Zuogui Jiangtang Tongmai Recipe;
type 2 diabetes;
cerebral infarction;
necroptosis
- From:
Chinese Traditional Patent Medicine
2024;46(9):2936-2942
- CountryChina
- Language:Chinese
-
Abstract:
AIM To investigate the effects of Zuogui Jiangtang Tongmai Recipe on necroptosis pathway in a rat model of type 2 diabetes mellitus(T2DM)complicated with cerebral infarction(CI).METHODS The SD rats were randomly divided into the sham operation group,the model group,the metformin group(0.045 g/kg),and the low,medium and high dose Zuogui Jiangtang Tongmai Recipe groups(6.5,13,26 g/kg),with 9 rats in each group.In contrast to rats of the sham operation group,rats of the other groups were given 4 weeks feeding of high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish a T2DM rat model with one week stable blood glucose,followed by gavage of corresponding drugs 3 days before the establishment of the middle cerebral artery occlusion(MCAO)model.After 7 days of administration,the rats had their CI injury assessed by mNSS method and TTC staining;their level of blood glucose detected by blood glucose meter;their levels of glycated serum protein,serum TNF-α and IL-1β detected by ELISA;their cerebral mRNA expressions of FADD,RIPK1,RIPK3 and MLKL detected by RT-qPCR;and their cerebral protein expressions of FADD,p-RIPK1,p-RIPK3 and p-MLKL detected by Western blot.RESULTS Compared with the sham operation group,the model group displayed increased levels of blood glucose value,glycosylated serum protein,neurological function score,cerebral infarction volume,cerebral FADD,RIPK1,RIPK3 and MLKL mRNA expressions,cerebral FADD,p-RIPK1,p-RIPK3 and p-MLKL protein expressions,serum TNF-α and IL-1β levels(P<0.01);and more disordered and morphologically diverse neurons with smaller nucleus.Compared with the model group,the groups intervened with medium or high dose Zuogui Jiangtang Tongmai Recipe,or metformin shared improvement in terms of the aforementioned indices(P<0.05,P<0.01);and more neurons with regular morphology neat arrangement,and reduced cell gap.CONCLUSION Zuogui Jiangtang Tongmai Recipe can improve the neurological dysfunction of the rat model of T2DM complicated with CI,which may associate with the inhibited activation of necroptosis signaling pathway.