Progesterone is neuroprotective against ischemic brain injury through its effects on the phosphoinositide 3-kinase/protein kinase B signaling pathway.
Progesterone is neuroprotective against ischemic brain injury through its effects on the phosphoinositide 3-kinase/protein kinase B signaling pathway.
复制标题
DOI：
10.1016/j.neuroscience.2012.03.008
复制
发表时间：
2012-05-17
期刊：
影响因子：
3.3
通讯作者：
Stein DG
中科院分区：
文献类型：
--
作者：
Ishrat T;Sayeed I;Atif F;Hua F;Stein DG
我们验证了磷脂酰肌醇-3激酶（PI 3 K/Akt）通路介导缺血性卒中后孕酮（PROG）的某些神经保护作用的假设。我们研究了PROG是否通过PI 3 K/Akt通路作用，可以影响血管内皮生长因子（VEGF）和脑源性神经营养因子（BDNF）的表达。通过电凝法对大鼠进行永久性局灶性脑缺血（pMCAO），并在闭塞后1h腹腔注射PROG（8 mg/kg）或载体，并在6、24和48 h皮下注射。在pMCAO后24 h，通过TUNEL测定、Western印迹和免疫组织化学分析PAkt/Akt水平、凋亡和凋亡相关蛋白（pBAD、BAD、caspase-3和切割的caspase-3）。在pMCAO后24、72小时和14天用Western印迹分析VEGF和BDNF。在pMCAO后，PROG治疗显著（p<0.05）减少缺血性病变大小和水肿。伤后24和72小时，PROG治疗组VEGF表达显著降低（p<0.05），14天后VEGF表达显著增加（p<0.05）。与单独的载体相比，治疗还增加了BDNF，并通过增加Akt磷酸化来减弱细胞凋亡。选择性PI 3 K抑制剂Wortmannin损害了PROG诱导的神经保护作用，并降低了缺血半暗带中pAkt水平的升高。我们的研究结果提示，PI 3 K/Akt通路通过改变脑内营养因子的表达，在介导脑卒中后PROG的神经保护作用中发挥作用。
We tested the hypothesis that the phosphatidylinositol-3 kinase (PI3K/Akt) pathway mediates some of the neuroprotective effects of progesterone (PROG) after ischemic stroke. We examined whether PROG acting through the PI3K/Akt pathway could affect the expression of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF). Rats underwent permanent focal cerebral ischemia (pMCAO) by electro-coagulation and received intraperitoneal injections of PROG (8mg/kg) or vehicle at 1h post-occlusion and subcutaneous injections at 6, 24, and 48h. PAkt/Akt levels, apoptosis and apoptosis-related proteins (pBAD, BAD, caspase-3, and cleaved caspase-3) were analyzed by TUNEL assays, Western blotting and immunohistochemistry at 24h post-pMCAO. VEGF and BDNF were analyzed at 24, 72h and 14 days post-pMCAO with Western blots. Following pMCAO, PROG treatment significantly (p<0.05) reduced ischemic lesion size and edema. Treatment with PROG significantly (p<0.05) decreased VEGF at 24 and 72h but increased VEGF expression 14d after injury. The treatment also increased BDNF, and attenuated apoptosis by increasing Akt phosphorylation compared to vehicle-alone. The selective PI3K inhibitor Wortmannin compromised PROG-induced neuroprotective effects and reduced the elevation of pAkt levels in the ischemic penumbra. Our findings lead us to suggest that the PI3K/Akt pathway can play a role in mediating the neuroprotective effects of PROG after stroke by altering the expression of trophic factors in the brain.
登录
查看更多内容
影响因子：
4.2
作者：
Kaur, Paramjit;Jodhka, Parmeet K.;Singh, Meharvan
通讯作者：
Singh, Meharvan
影响因子：
8.3
作者：
KRUPINSKI, J;KALUZA, J;WANG, JM
通讯作者：
WANG, JM
影响因子：
4.2
作者：
Djebaili, M;Guo, QM;Stein, DG
通讯作者：
Stein, DG
DOI：
10.1007/bf02189960
发表时间：
1993-03-01
影响因子：
4.7
作者：
DELCKER, A;DIENER, HC;FAUSTMANN, P
通讯作者：
FAUSTMANN, P
影响因子：
3
作者：
Guerra-Araiza, Christian;Amorim, Miguel A. R.;Garcia-Segura, Luis M.
通讯作者：
Garcia-Segura, Luis M.