1.Influence of PJ34 on the Expression of MMP-9 and Claudin-5 in Rat with Focal Cerebral Ischemia Reperfusion Injury
Penglian WU ; Yan LI ; Xinhui FU ; Lianghe DU ; Dongyu WANG
Journal of China Medical University 2015;44(8):694-698,703
Objective To investigate the effects of PJ34,a poly ADP-ribose polymerase(PARP)inhibitor,on the expression of matrix metallopro-teinases-9( MMP-9 )and Claudin-5 in ischemic cortex of rats with focal cerebral ischemia-reperfusion(I/R)injury. Methods The focal cerebral ischemia-reperfusion model of middle cerebral artery occlusion(MCAO)was established by intraluminal suture . PJ34 was injected intraperitoneal-ly. Blood-brain barrier(BBB)permeability was quantitatively determined by Evans blue assay. Infarct volume changes were observed by 2,3,5-tri-phenyltetrazolium chloridedyeing(TTC)staining. The expression of the MMP-9 and Claudin-5 in rats of cerebral cortex were measured by immuno-histochemistry assay and western blot analysis . Results Compared with sham group,the expression of MMP-9,the contents of EB and infarct vol-ume increased progressively over time after I/R,and reached maximum levels at 48 h(P<0.05);The expression of Claudin-5,the contents of EB and infarct volume reduced significantly over time after I/R,and reached the minimum levels at 48 h in model group(P<0.05). Compared with model group,the expression of MMP-9,the contents of EB and infarct volume was reduced significantly and the expression of Claudin-5,the con-tents of EB and infarct volume was increased at the same time point in PJ34 group(P<0.05). Conclusion PJ34 maintained the blood-brain barri-er permeability by inhibiting the expression of MMP-9,and increasing the expression of Claudin-5,which had neuroprotection on cerebral ischemia-reperfusion injury.
2.Influence of Poly (ADP-ribose) Polymerase Inhibitor PJ34 on Blood Brain Barrier in Rats with Cerebral Ischemia-reperfusion Injury
Yan LI ; Penglian WU ; Lianghe DU ; Xinhui FU ; Dongyu WANG
Journal of China Medical University 2015;44(8):709-713
Objective To investigate the influence of poly(ADP-ribose)polymerase inhibitor PJ34 on blood brain barrier(BBB)in rats with cere-bral ischemia-reperfusion injury. Methods Rat model of cerebral ischemia-reperfusion injury was established by the middle cerebral artery occlu-sion. A total of 135 SD rats were randomly divided into 3 groups:sham-operated group(sham group),ischemia-reperfusion group(IR group)and PJ34 group(PJ34 group). 45 animals in each group were then equally divided into subgroups and the rats were sacrificed at 6 h,24 h,48 h after re-perfusion,respectively. BBB permeability was evaluated by detection of extravasated Evans blue(EB). The expression of tumor necrosis factorα(TNF-α)and matrix metalloproteinase 9(MMP-9)activity were measured by immunohistochemistry and western blot at different time points. Re?sults Compared with sham group,the contents of EB and the expressions of TNF-αand MMP-9 in IR group were increased significantly(P<0.05). Compared with IR group,the contents of EB and the expressions of TNF-αand MMP-9 in PJ34 group were markedly decreased at the same time point(P<0.05). Conclusion The present study provided in vivo evidence that PARP inhibitor PJ34 can protect against cerebral ischemia re-perfusion injury,and the mechanism might be related to maintaining the stability of blood-brain barrier by suppressing the expression of TNF-αand MMP-9 in ischemic cortex.
3.The impact of in-hospital pneumonia on the risk of in-hospital and long-term mortality in patients with acute ischemic stroke
Penglian WANG ; Xingquan ZHAO ; Yilong WANG ; Zhonghua YANG ; Anxin WANG ; Yongjun WANG
Chinese Journal of Internal Medicine 2013;(7):554-557
Objective To observe the short-term and long-term impacts of in-hospital pneumonia on outcomes of patients hospitalized with acute ischemic stroke.Methods All consecutive patients older than 18 years with acute ischemic stroke were prospectively recruited to this study,including 132 clinical centers in 32 provinces and 4 municipalities (including Hong Kong region) in China from September 2007 to August 2008.Case report form was designed.Data of pneumonia and survival outcomes at baseline ; discharge ; 3,6 and 12 months after admission were recorded.Multivariable logistic regression was used for statistical correlation analysis.Results A total of 1373 (11.88%) patients from 11 560 acute ischemic stroke patients were notified with in-hospital pneumonia.The case fatality rate was 14.4% (1664 patients) within 12 months after stroke onset.The fatality rate in patients with pneumonia was higher than that of patients without pneumonia.In-hospital pneumonia was an independent risk factor for death at discharge (adjusted OR =5.916 ; 95% CI 4.470-7.831),at 3 months (adjusted OR =3.641 ; 95% CI 3.035-4.367),6 months (adjusted OR =3.445 ; 95% CI 2.905-4.086),and 12 months (adjusted OR =3.543 ; 95% CI 3.016-4.161) after onset.Conclusion In-hospital pneumonia is an adverse factor for the short-term and longterm survival of acute ischemic patients in China.