PTEN抑制剂Bpv(HOpic)对大鼠缺血脑损伤的作用及机制  

ROLE AND MECHANISM OF ACTION OF THE PTEN INHIBITOR BPV(HOPIC)IN RATS WITH ISCHEMIC BRAIN INJURY

作　　者：任近阳 姚旭进 孙江东 胡文杰[1] 孔祥一 万芪 REN Jinyang;YAO Xujin;SUN Jiangdong;HU Wenjie;KONG Xiangyi;WAN Qi(Institute of Neuroregeneration&Neurorehabilitation,Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学神经再生与康复研究院,山东青岛266071

出　　处：《青岛大学学报（医学版）》2022年第5期633-638,共6页Journal of Qingdao University(Medical Sciences)

基　　金：国家自然科学基金资助项目(82071385)。

摘　　要：目的探讨第10号染色体缺失的张力蛋白同源磷酸酶基因(PTEN)-Jumonji-C结构域蛋白5(JMJD5)信号通路在缺血性脑损伤中的作用,探索潜在的神经保护治疗措施。方法构建大鼠大脑中动脉栓塞(MCAO)模型,Western blot检测缺血损伤脑组织中PTEN和JMJD5蛋白表达水平变化。构建PTEN过表达和干扰模型,Western blot检测脑组织中JMJD5蛋白表达的变化。构建JMJD5过表达和干扰模型,2,3,5-氯化三苯基四氮唑(TTC)染色观察脑梗死面积的变化。给予MCAO大鼠PTEN抑制剂Bpv(HOpic),Western blot检测缺血损伤脑组织中JMJD5蛋白水平的变化。通过改良神经功能缺损程度评分(mNSS)评估下调JMJD5表达对Bpv(HOpic)神经保护作用的影响。结果随缺血损伤时间延长,MCAO 3、6、9 h组大鼠脑组织中PTEN蛋白表达水平逐渐升高,JMJD5蛋白表达水平逐渐下降,与假手术组比较差异均有显著性(F=20.70、15.41,t=2.13~7.28,P<0.05)。过表达PTEN后脑组织中JMJD5蛋白水平明显下降,而干扰PTEN表达后JMJD5水平明显升高(F=14.10,t=3.88、2.88,P<0.05)。JMJD5表达上调使脑梗死面积减小,而JMJD5表达下调使梗死面积增加(F=10.58,t=3.92、2.38,P<0.05)。MCAO大鼠给予Bpv(HOpic)处理后损伤脑组织中JMJD5蛋白表达水平增加(t=3.32,P<0.05)。Bpv(HOpic)干预14 d可使MCAO大鼠mNSS得分明显降低,而下调JMJD5表达可阻断此作用(F=4.19,q=6.69、6.16,P<0.05)。结论缺血损伤脑组织中PTEN表达增加,JMJD5表达下降。PTEN抑制剂Bpv(HOpic)可能通过上调JMJD5的表达改善大鼠神经功能缺陷。Bpv(HOpic)调控PTEN-JMJD5信号通路可能是一种潜在的神经保护治疗措施。Objective To investigate the role of the phosphatase and tensin homolog deleted on chromosome 10(PTEN)-Jumonji C-domain-containing 5(JMJD5)signaling pathway in ischemic brain injury and potential neuroprotective treatment measures.Methods A rat model of middle cerebral artery occlusion(MCAO)was established,and Western blot was used to measure the changes in the protein expression levels of PTEN and JMJD5 in ischemic brain tissue.A rat model of PTEN overexpression or interference was established,and Western blot was used to measure the change in the protein expression of JMJD5 in brain tissue.A rat model of JMJD5 overexpression or interference was established,and 2,3,5-triphenyltetrazolium chloride staining was used to observe the change in cerebral infarct area.MCAO rats were given the PTEN inhibitor Bpv(HOpic),and Western blot was used to measure the change in the protein expression level of JMJD5 in ischemic brain tissue.Modified Neurological Severity Score(mNSS)was used to assess the influence of JMJD5 knockdown on the neuroprotective effect of Bpv(HOpic).Results Compared with the sham-operation group,the 3-,6-,and 9-hour MCAO groups had a gradual increase in the protein expression of PTEN and a gradual reduction in the protein expression of JMJD5 in brain tissue over the time of ischemic injury(F=20.70,15.41;t=2.13-7.28;P<0.05).There was a significant reduction in the protein expression level of JMJD5 in brain tissue after PTEN overexpression,but there was a significant increase in the protein expression level of JMJD5 after PTEN interference(F=14.10;t=3.88,2.88;P<0.05).JMJD5 upregulation reduced cerebral infarct area,whereas JMJD5 downregulation increased infarct area(F=10.58;t=3.92,2.38;P<0.05).After Bpv(HOpic)treatment in MCAO rats,there was a significant increase in the protein expression level of JMJD5 in ischemic brain tissue(t=3.32,P<0.05).After 14 days of intervention with Bpv(HOpic),there was a significant reduction in mNSS score in MCAO rats,which was blocked by downregulating the expression of JMJD

关 键 词：PTEN磷酸水解酶 含Jumonji结构域组蛋白脱甲基酶类 蛋白酶抑制药 卒中 脑缺血 神经保护 大鼠 

分 类 号：R338.2[医药卫生—人体生理学] R743.3[医药卫生—基础医学]