Sinomenine hydrochloride attenuates renal hemodynamics and microcircu-lation disturbance in db/db mice by inhibiting DAG/PKC signaling pathway
10.3969/j.issn.1000-4718.2025.01.009
- VernacularTitle:基于DAG/PKC信号通路探讨盐酸青藤碱对db/db小鼠肾脏血流动力学及微循环障碍的影响
- Author:
Junguang LIU
1
;
Meng LI
;
Xiaohan CHEN
;
Zhili FENG
;
Xiaohong ZHOU
;
Xiangmei CHEN
;
Weijuan GAO
Author Information
1. 承德医学院病理生理学教研室,河北 承德 067000
- Publication Type:Journal Article
- Keywords:
sinomenine hydrochloride;
diabetic kidney disease;
hemodynamics;
microcirculation;
DAG/PKC signaling pathway
- From:
Chinese Journal of Pathophysiology
2025;41(1):72-80
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To explore the effect of sinomenine hydrochloride(SH)on microcirculation and renal func-tion in type 2 diabetic db/db mice with a focus on the diacylglycerol(DAG)/protein kinase C(PKC)signaling pathway.METHODS:Eighteen 6-week-old male db/db mice were randomly divided into three groups:model group(saline),LY group(administered with 1 mg·kg-1·d-1 LY333531),and SH group(administered with 124.8 mg·kg-1·d-1 SH).Addi-tionally,6 age-matched db/m mice comprised the control group(saline).Daily intragastric administration lasted 6 weeks.Body mass,fasting blood glucose(FBG),urinary microalbumin(mALB),urinary creatinine(UCr)and urinary β2-micro-globulin(β2-MG)were measured in each group.The serum levels of endothelin-1(ET-1),endothelial nitric oxide syn-thase(eNOS),collagen type Ⅳ(Col Ⅳ)and laminin(LN),and the levels of DAG and PKC in renal tissues were ana-lyzed by enzyme-linked immunosorbent assay(ELISA).The morphological changes of renal tissues were assessed using HE and PAS staining,and kidney ultrastructure was examined via transmission electron microscopy.Immunohistochemis-try and Western blot were used to detect PKC and p-PKC levels in renal tissues.RESULTS:Compared with model group,the mice in both LY and SH groups showed decreased body mass(P＜0.05),with significantly reduced FBG level in LY group(P＜0.01).In addition,the urinary mALB and β2-MG levels were markedly decreased(P＜0.01),while UCr level was significantly increased(P＜0.01).Serum ET-1,Col Ⅳ and LN levels were significantly lower(P＜0.01),whereas eNOS level was notably higher(P＜0.01).Renal tissue DAG and PKC levels,as well as p-PKC expression were significantly reduced(P＜0.01).Improvements in renal tissue pathology and ultrastructure were observed.CONCLU-SION:Sinomenine hydrochloride improves microcirculation in diabetic db/db mice by modulating DAG/PKC signaling pathway,thus exerting protective effect on the kidney.
