title: Reduction in ischemic cerebral infarction is mediated through golgi phosphoprotein 3 and Akt/mTOR signaling following salvianolate administration.
abstract: Salvianolate has been reported to possess protective properties. However, its specific mechanisms have yet to be identified. Our study aimed to identify the molecular mechanism of antioxidative stress function of salvianolate on rat ischemia and reperfusion brain tissues. Rats were randomly distributed into three experimental groups: sham, model and intervention . All animal neurobehavioral tests were performed at the end of 72-h reperfusion per Longa's method, and rats with a score of 0 (no neurological deficit) or 4 (severe neurological deficit with impaired consciousness) were excluded. Brain slices were obtained after 72 h of reperfusion and stained with triphenyltetrazolium chloride. Western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine levels of GOLPH3, Akt/p-Akt, and mTOR/p-mTOR expressions in ischemic cortex. Salvianolate (18mg/kg intraperitoneal injection) significantly decreased the neurological deficit scores of rats in groups of 72 h I/R and reduced the number of TUNELpositive cells in the cerebral cortex when given at onset and at 24 and 48 h after reperfusion, leading to decreased cerebral infarction in rats after ischemia/reperfusion injury. Results of Western blot and qRT-PCR showed that salvianolate could significantly upregulate the expression of Golgi phosphoprotein-3 as well as the phosphorylation of Akt and mTOR. Above findings indicate that salvianolate exerts potent and long-term neuroprotective effects in the model of cerebral I/R, and Golgi phosphoprotein-3 and its downstream activation of Akt/mTOR signaling pathway may provide a new insight for the antioxidative effect of salvianolate.
authors.forename: Hong
authors.initials: H
authors.lastname: You
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Jinnan
authors.initials: J
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lei
authors.forename: Xi
authors.initials: X
authors.lastname: Tao
authors.forename: Pinghui
authors.initials: P
authors.lastname: Xie
authors.affiliation: Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, P.R. China. luwei03380338@gmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002544:Cerebral Infarction / Q000378:metabolism* / Q000517:prevention & control; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D002352:Carrier Proteins; C424602:GMx33alpha protein, rat; D018696:Neuroprotective Agents; D010936:Plant Extracts; D011993:Recombinant Fusion Proteins; C561960:salvianolate; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases