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Effects of salvia polyphenolic acids combined with panax notoginseng saponins on cerebral ischemia-reperfusion injury in rats by regulating M1/M2 microglia polarization
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DOI   10.11656/j.issn.1672-1519.2020.07.26
Key Words   salvia polyphenolic acids;panax notoginseng saponins;microglia;polarization;cerebral ischemia-reperfusion injury
Author NameAffiliationE-mail
JIA Zhuangzhuang Research Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin Key Laboratory of Chinese Medicine Pharmacology, Key Laboratory of Formulae, Ministy of Education, Tianjin 301617, China  
CHEN Hongyang Research Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin Key Laboratory of Chinese Medicine Pharmacology, Key Laboratory of Formulae, Ministy of Education, Tianjin 301617, China  
ZHAO Lei Research Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin Key Laboratory of Chinese Medicine Pharmacology, Key Laboratory of Formulae, Ministy of Education, Tianjin 301617, China  
YUAN Qing Research Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin Key Laboratory of Chinese Medicine Pharmacology, Key Laboratory of Formulae, Ministy of Education, Tianjin 301617, China  
YIN Menglan Research Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin Key Laboratory of Chinese Medicine Pharmacology, Key Laboratory of Formulae, Ministy of Education, Tianjin 301617, China  
WANG Shaoxia Research Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin Key Laboratory of Chinese Medicine Pharmacology, Key Laboratory of Formulae, Ministy of Education, Tianjin 301617, China  
HU Limin Research Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin Key Laboratory of Chinese Medicine Pharmacology, Key Laboratory of Formulae, Ministy of Education, Tianjin 301617, China hulimin@tjutcm.edu.cn 
Abstract
    [Objective] To investigate the effect of salvia polyphenolic acids combined with panax notoginseng saponins on cerebral ischemia-reperfusion injury in rats by adjusting the polarization of M1/M2 microglia.[Methods] The occlusion model of middle cerebral artery was established by thread embolism method. Sixty male Wistar rats were randomly divided into sham operation group (Sham),ischemia-reperfusion group (I/R),edaravone group (Eda,6 mg/kg),salvia polyphenolic acids group (SPA,21 mg/kg),panax notoginseng saponins group (PNS,100 mg/kg),salvia polyphenolic acids combined with panax notoginseng saponins group (SPA+PNS,21 mg/kg+100 mg/kg),tail vein injection once a day,Sham group and I/R injection with equal volume of normal saline,after continuous administration for 5 days,the changes of cerebral blood flow,neurological function score and histomorphology of rats were observed. Nissl staining and neuroribonucleoprotein (NeuN) immunofluorescence staining were used to observe neuronal damage. CD16/Iba-1 and CD206/Iba-1 immunofluorescence double staining were used to detect the phenotypes of M1 and M2 microglia in ischemic penumbra. Western-blot assay was used to detect the protein expressions of M1 microglial markers interleukin-1β (IL-1β),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),inducible nitric oxide synthase (iNOS),M2 microglial marker CD206,transforming growth factor-β (TGF-β) and interleukin-10 (IL-10).[Results] Compared with I/R group,SPA group,PNS group and SPA+PNS group have improved to varying degrees in cerebral blood flow,nerve function defect,tissue morphology and neuronal damage,and promoted the expression of CD206/Iba-1 in M2 microglial cells,and up-regulated the protein expression of CD206,TGF-β and IL-10. Inhibition of M1 microglia CD16/Iba-1 expression,down-regulation of IL-1β,IL-6,TNF-α,iNOS protein expression,and SPA+PNS group improved better than SPA group,PNS group.[Conclusion] Salvia polyphenolic acids,panax notoginseng saponins and their compatibility can reduce cerebral ischemia-reperfusion injury in rats,and the compatibility application effect is better than that of single application. The mechanism may be related to promoting the conversion of M1 type polarization to M2 type polarization of microglia.

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