Mechanism of Naoxintong Capsules Against Ischemia-reperfusion Injury in Rats via Inhibiting Pericyte Contraction Based on RHOA/ROCK1 Pathway
10.13422/j.cnki.syfjx.20250239
- VernacularTitle:基于RHOA/ROCK1通路探讨脑心通胶囊抑制大鼠脑缺血再灌注损伤中周细胞收缩机制
- Author:
Yinlian WEN
1
;
Jinfeng SHANG
1
;
Bohong WANG
1
;
Wanting WEI
1
;
Xiaolu ZHANG
1
;
Guijinfeng HUANG
1
;
Xin LIU
1
Author Information
1. School of Chinese Materia Medica， Beijing University of Chinese Medicine， Beijing 102488， China
- Publication Type:Journal Article
- Keywords:
Naoxintong capsules;
ischemia-reperfusion （I/R） injury;
pericyte contraction;
Ras homolog family member A （RHOA）/Rho-associated coiled-coil containing protein kinase 1 （ROCK1） pathway;
pharmacological mechanism
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(12):159-167
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the mechanism of Naoxintong capsules on ischemia-reperfusion （I/R） injury in rats based on the changes of pericytes mediated by Ras homolog family member A （RHOA）/Rho-associated coiled-coil containing protein kinase 1 （ROCK1） pathway. MethodsNinety rats （15 rats for each group） were randomly divided into a sham operation group， a model group， a positive control group receiving Ginkgo biloba extract （21.6 mg·kg-1）， and groups receiving Naoxintong capsules at low， medium， and high doses of 55， 110， and 220 mg·kg-1 （NXT-L， NXT-M， and NXT-H groups）， respectively. Except for those in the sham operation group， all rats were subjected to transient middle cerebral artery occlusion （tMCAO） to establish the experiment model. Nerve function was assessed using a neurological function score. Cerebral blood flow was detected using a laser speckle contrast imager， and the cerebral infarction rate was calculated using 2，3，5-Triphenyl tetrazolium chloride （TTC） staining. Pathological changes were observed by hematoxylin-eosin （HE） staining and Nissl staining， while pericyte morphology was observed via transmission electron microscopy. Blood-brain barrier destruction was observed by Evans blue staining. Albumin and ischemia-modified albumin levels were measured using assay kits. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels of RHOA， ROCK1， platelet-derived growth factor receptor β （PDGFRB）， α-smooth muscle actin （α-SMA）， tight junction protein （ZO-1）， matrix metalloproteinase-2 （MMP-2）， and matrix metalloproteinase-9 （MMP-9）. ResultsCompared with the sham operation group， the model group exhibited decreased neurological function scores， higher percentage reduction in blood flow， and increased cerebral infarction rates （P<0.01）. Additionally， cortical neuronal nucleus shrinkage， edema， a decreased number of Nissl bodies， reduced pericyte area， elevated albumin content in the cortex （P<0.05）， and increased ischemic modified albumin levels （P<0.01） were observed. The mRNA and protein expression levels of RHOA， ROCK1， PDGFRB， α-SMA， MMP-2， and MMP-9 were increased （P<0.01）， while those of ZO-1 were decreased. Compared with the model group， all treatment groups showed improved neurological function scores， lower percentage reduction in blood flow， reduced cerebral infarction rates （P<0.01）， alleviated cortical histological changes， increased number of Nissl bodies， expanded pericyte area， decreased albumin content in the cortex， and reduced ischemia-modified albumin levels （P<0.01）. The mRNA and protein expression levels of RHOA， ROCK1， PDGFRB， α-SMA， MMP-2， and MMP-9 were decreased （P<0.01）， while those of ZO-1 were increased. Among the treatment groups， the NXT-M group showed the most pronounced improvement in cerebral I/R injury. ConclusionNaoxintong capsules can restore cerebral blood supply， reduce microcirculation disturbance， and protect blood-brain barrier in rats with I/R injury. Its mechanism of action may be related to the inhibition of the RHOA/ROCK1 signaling pathway and reduced pericyte contraction.
