Toddalia asiatica attnuates cerebral ischemia-reperfusion injury in rats through modulating M1/M2 polarization of microglia
10.3969/j.issn.1000-4718.2023.12.003
- VernacularTitle:飞龙掌血通过调控大鼠M1/M2型小胶质细胞极化减轻脑缺血再灌注损伤
- Author:
Jianhong GAO
1
;
Gang WANG
;
Dan YANG
;
Fangyu ZHAO
;
Yiduo HE
;
Xian-Bing CHEN
Author Information
1. 风湿性疾病发生与干预湖北省重点实验室,湖北省肾脏病临床医学研究中心,湖北民族大学医学部,湖北 恩施 445000
- Keywords:
Toddalia asiatica;
cerebral ischemia-reperfusion injury;
microglia;
neuroinflammation;
apopto-sis
- From:
Chinese Journal of Pathophysiology
2023;39(12):2133-2140
- CountryChina
- Language:Chinese
-
Abstract:
AIM:Observation of neuroprotective effects of Toddalia asiatica(TA)on cerebral ischemia-reper-fusion injury(CIRI)in rats by investigating the effects and mechanisms of drugs on the polarization of microglia M1/M2 subtype and the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)path-way.METHODS:The modified thread occlusion method was used to establish a rat model of CIRI,and the rats were ran-domly divided into the model group,Toddalia asiatica(1.08 g/kg)group,donepezil hydrochloride(0.45 mg/kg)group,and sham group,with 16 rats in each group.Based on the assessment of neurofunctional changes in each group of rats,HE and Nissl staining were used to observe the pathological changes in brain tissue.TUNEL staining was performed to de-tect neuronal apoptosis,immunohistochemistry was used to detect the expression of M1 microglia marker ionized calcium-binding adapter molecule 1(Iba1),M2 microglia marker arginase 1(Arg1),and TLR4 localization.Western blot was used to detect the expression of microglia polarization proteins and proteins related to TLR4/MyD88/NF-κB pathway in the hippocampus region.RESULTS:Compared with sham group,the model group rats had higher neurological function scores(P＜0.01),and neuronal arrangement in the hippocampus and cortex was loose and disordered,Nissl bodies de-creased,and neuronal apoptosis increased.The numbers of M1 microglia marker Iba1-,M2 microglia marker Arg1-,and TLR4-positive cells were significantly increased.In addition,the protein levels of TLR4,MyD88,p-NF-κB p65,NF-κB p65,p-NF-κB inhibitory factor(p-IκB),Iba1,interleukin-6(IL-6),and Arg1 in the hippocampus were elevated(P＜0.05),while IL-4 and IL-10 expression were decreased(P＜0.01).Compared with model group,the Toddalia asiatica group and Donepezil hydrochloride group showed increased protein expression of Arg1,IL-4 and IL-10(P＜0.05),while the other indicators were decreased(P＜0.05,P＜0.01).CONCLUSION:Toddalia asiatica possesses neuroprotective effects on CIRI rats,which may be attributed to its ability to regulate M1/M2 polarization and inhibit the TLR4/MyD88/NF-κB-mediated inflammatory pathway.
