Interaction between sex and apolipoprotein e genetic background in a murine model of intracerebral hemorrhage.
Interaction between sex and apolipoprotein e genetic background in a murine model of intracerebral hemorrhage.
复制标题
DOI：
10.1007/s12975-012-0176-7
复制
发表时间：
2012-03
影响因子：
6.9
通讯作者：
James, Michael L.
中科院分区：
文献类型：
--
作者：
Lei, Beilei;Mace, Brian;Bellows, Steven T.;Sullivan, Patrick M.;Vitek, Michael P.;Laskowitz, Daniel T.;James, Michael L.
新的证据表明，性别和载脂蛋白E(APOE)基因型分别影响脑出血(ICH)后的预后。我们验证了性别和载脂蛋白E基因多态性之间存在相互作用的假说，以改变脑出血后的预后，并通过注射外源载脂蛋白E模拟多肽而改变。为了明确性别和载脂蛋白E基因多态性对脑出血的影响，我们在胶原酶诱导的雄性和雌性APOETR小鼠(APOE3或APOE4等位基因纯合的靶向替换小鼠；n=12/组)中建立了胶原酶诱导的脑出血模型，并评估了在旋转(RR)和Morris水迷宫(MWM)中的表现。伤后24小时苏木精-伊红染色观察血肿形成情况(n=8)。采用单独队列(n=12个/组)，脑出血后给予载脂蛋白E模拟肽(COG1410，2 mg/kg)，用RR和MWM对小鼠进行评估。通过脑出血后7天(RR)和32天(MWM)的测试，雌性小鼠在RR和MWM方面的表现优于雄性小鼠190%以上(p<；0.01)。与所有其他组相比，雌性APOE3tr小鼠在伤后24小时的血肿体积无明显差异(p<；0.05)。给予治疗性apoE模拟肽可以改善雄性和雌性apo4tr小鼠脑出血后7天的RR潜伏期和雄性apo4tr小鼠脑出血后28-32天的MWM潜伏期(p<；0.05)。在我们的脑出血小鼠模型中，性别和载脂蛋白E基因多态性影响功能结果。此外，损伤后给予外源性载脂蛋白E类似肽可以不同地改变性别和载脂蛋白E多态之间的相互作用。
Emerging evidence suggests sex and apolipoprotein E (APOE) genotype separately modify outcomes after intracerebral hemorrhage (ICH). We test the hypothesis that an interaction exists between sex and APOE polymorphism in modifying outcomes after ICH and is altered by administration of exogenous apoE-mimetic peptide. To define the effects of sex and APOE polymorphism in ICH, we created collagenase-induced ICH in male and female APOETR mice (targeted replacement mice homozygous for APOE3 or APOE4 alleles; n=12/group) and assessed performance on Rotarod (RR) and Morris water maze (MWM). To evaluate hematoma formation, we used hematoxylin and eosin staining at 24 h after injury (n=8/group). Using separate cohorts (n=12/group), apoE-mimetic peptide (COG1410 at 2 mg/kg) was administered after ICH, and mice were assessed by RR and MWM. Female mice outperformed male mice via RR and MWM by over 190% improvement through 7 days (RR) and 32 days (MWM) of testing after ICH (p<0.01). Female APOE3TR mice demonstrated improved function compared with all other groups (p<0.05) without any difference in hematoma volume at 24 h after injury in any group. Administration of a therapeutic apoE-mimetic peptide improved RR latencies through 7 days after ICH in male and female APOE4TR mice and MWM latencies over days 28–32 after ICH in male APOE4TR mice (p<0.05). Sex and APOE polymorphism influence functional outcomes in our murine model of ICH. Moreover, administration of exogenous apoE-mimetic peptide after injury differentially modifies the interaction between sex and APOE polymorphism.
登录
查看更多内容
影响因子：
4.2
作者：
HAMM, RJ;PIKE, BR;JENKINS, LW
通讯作者：
JENKINS, LW
影响因子：
1.2
作者：
Kimura, Y;Takishita, S;Fukiyama, K
通讯作者：
Fukiyama, K
影响因子：
3.5
作者：
Laskowitz, D. T.;Fillit, H.;Vitek, M. P.
通讯作者：
Vitek, M. P.
影响因子：
5.3
作者：
Laskowitz, DT;Thekdi, AD;Bennett, ER
通讯作者：
Bennett, ER
影响因子：
3.5
作者：
Gao, Junling;Wang, Haichen;Laskowitz, Daniel T.
通讯作者：
Laskowitz, Daniel T.