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.Correlation between serum ischemia modified albumin and calmodulin expression levels and neurological impairment in patients with cerebral small vessel disease
Lianghe DU ; Guohao ZHAO ; Qiaoyan LI
Chinese Journal of Primary Medicine and Pharmacy 2024;31(1):23-28
Objective:To investigate the correlation between serum ischemia modified albumin (IMA) and calmodulin (CaM) expression levels and neurological impairment in patients with cerebral small vessel disease.Methods:The clinical data of 140 patients with cerebral small vessel disease (CSVD) who received treatment at The Third People Hospital in Liaocheng between April 2020 and December 2021 were retrospectively analyzed. On admission, serum levels of CaM and IMA were measured using an enzyme-linked immunosorbent assay and an albumin-cobalt binding test. Patients' neurological function was evaluated using the National Institutes of Health Stroke Scale (NIHSS). Patients' transient cerebral ischemia, urinary incontinence, and gait disturbance were evaluated using the National Institute of Neurological Disorders and Stroke Scale. Patients' cognitive function was evaluated using the Montreal Cognitive Assessment scale. The influential factors of serum IMA and CaM expression levels in patients with CSVD were analyzed. The factors that affect the severity of neuological imairment in patients with CSVD and their correlation with serum IMA and CaM expression levels were analyzed.Results:The gender, age, presence or absence of gait disorders, and presence or absence of urinary incontinence of patients were not correlated with serum IMA and CaM levels (all P > 0.05). The serum levels of IMA [(38.5 ± 5.3) × 103U/L, (38.5 ± 4.7) × 103U/L, (39.0 ± 4.4) × 103U/L] and CaM [(190.4 ± 34.5) μg/L, (191.2 ± 26.7) μg/L, (199.7 ± 24.8) μg/L] in patients with cognitive impairment, dizziness and vertigo, and transient cerebral ischemia were significantly higher than those in patients with normal cognitive function, patients without dizziness and vertigo, or patients without transient cerebral ischemia [(27.3 ± 4.4) × 103U/L, (21.0 ± 3.8) × 103U/L, (20.5 ± 5.1) × 103U/L, (180.6 ± 29.6) μg/L, (179.5 ± 28.6) μg/L, (168.6 ± 32.4) μg/L, t = 14.10, 24.36, 22.50, all P < 0.05]. There were significant differences in cognitive impairment (38/16/9), dizziness and vertigo (39/16/8), transient cerebral hemorrhage (35/16/9), NIHSS score [(3.6 ± 0.8) points, (7.5 ± 0.9) points, (16.2 ± 3.2) points], CaM levels [(125.3 ± 20.5) μg/L, (185.5 ± 23.6) μg/L, (237.9 ± 54.3) μg/L], and IMA levels [(21.2 ± 3.5)] × 103 U/L, [(38.5 ± 4.3) × 103 U/L, (74.9 ± 5.4) × 103 U/L] among patients with mild, moderate, and severe neurological impairment ( t = 32.87, 11.28, 12.42, 34.59, 151.73, 147.84, all P < 0.05). The results of multivariate analysis indicated that cognitive impairment ( OR = 1.578, 95% CI: 1.043-2.386), transient cerebral ischemia ( OR = 2.396, 95% CI: 1.156-4.969), dizziness and vertigo ( OR = 1.906, 95% CI: 1.086-3.345), NIHSS score ( OR = 2.171, 95% CI: 1.162-4.056), CaM level ( OR = 2.022, 95% CI: 1.268-3.224), and increased IMA levels ( OR = 2.090, 95% CI: 1.313-3.325) were independent influential factors for worsened neurological impairment (all P < 0.05). The serum levels of IMA and CaM in patients with CSVD were significantly positively correlated with the severity of neurological impairment ( r = 5.45, 8.33, both P < 0.05). Conclusion:The elevated serum levels of IMA and CaM in patients with CSVD serve as independent risk factors for neurological impairment, and these levels are positively correlated with the severity of neurological impairment.
4.Proportion and related influencing factors of HIV-infected individuals that rejecting the antiretroviral therapy among all the HIV infections, Dehong prefecture, Yunnan province.
Shitang YAO ; Runhua YE ; Yuecheng YANG ; Lifen XIANG ; Jibao WANG ; Benli DU ; Wenxiang HAN ; Yongying NIE ; Zhongju YANG ; Weimei LI ; Na HE ; Song DUAN
Chinese Journal of Epidemiology 2014;35(12):1324-1328
OBJECTIVETo examine the proportion and influencing factors on HIV-infected individuals who rejecting the antiretroviral therapy among all the HIV positives, in Dehong prefecture, Yunnan province.
METHODSA cross-sectional analysis was conducted on all the local HIV-infected survivals aged over 16 year old who refused to receive antiretroviral therapy (ART) by the end of 2013 in Dehong prefecture.
RESULTSThe proportion of those rejecting the ART among HIV-infected survivals and aged over 16 years old in Dehong prefecture, was 7.4% (605/8 136). Factors related to the 'rejection' among the 605 refusals would include: being male (72.9%), aged 31-45 years (57.2%), peasants (75.4%), married (52.2%), with minor ethnicity (41.3%), illiterate or only having primary school education (58.7%), infected through sexual contacts (61.2%), and with CD4(+)T cell counts >350 cells/mm(3) (66.6%). Data from the multiple logistic regression analysis indicated that rejecting the ART was significantly associated with areas, gender, age, ethnicity and CD4(+)T cell counts of the HIV patients. Those who were from Yingjiang county, female, aged 31-45 years old had lower proportions of ART refusals than those who were from Ruili city, male, aged ≤30 year old. Those who were of Dai minority and had no records on CD4(+)T cell counts, had higher proportions of ART refusals than those who were of Han ethnicity and had CD4(+)T cell counts ≤350 cells/mm(3). Reasons for the 605 HIV-infected patients with rejection to the ART would include fear of disclosure of HIV infection status (84, 13.9%), misunderstandings of the effectiveness and side effects of ART (111, 18.3%), self-realized wellness(340, 56.2%) and others (70, 11.6%). Of them, reasons for the 181 patients with CD4(+)T cell counts ≤350 cells/mm(3) that rejecting ART would include fearfulness on the disclosure of HIV infection status(40, 22.1%), misunderstandings of the effectiveness and side effects of ART (36, 19.9%), self-realized wellness (84, 46.4%) and others (21, 11.6%). Among those who rejected ART, reasons for that would vary by areas, gender, age, marital status and routes of HIV transmission, according to the results from Chi-squared tests.
CONCLUSIONA substantial proportion of HIV-infected individuals rejected ART in Dehong prefecture of Yunnan province. It was urgently needed to enhance health education programs of ART tailored for those HIV-infected patients, according to different characteristics and reasons for rejection, so as to promote the ART in this prefecture.
Adult ; Anti-Retroviral Agents ; therapeutic use ; China ; Cross-Sectional Studies ; Ethnic Groups ; Female ; HIV Infections ; drug therapy ; Health Education ; Health Services Needs and Demand ; Humans ; Male ; Marital Status ; Marriage ; Middle Aged ; Minority Groups ; Sexual Behavior ; Treatment Refusal