Carswell H V, Anderson N H, Clark J S, Graham D, Jeffs B, Dominiczak A F, Macrae I M
Wellcome Surgical Institute, Department of Statistics, University of Glasgow (Scotland, UK).
Hypertension. 1999 Feb;33(2):681-5. doi: 10.1161/01.hyp.33.2.681.
We have investigated genetic transmission of increased sensitivity to focal cerebral ischemia and the influence of gender in the stroke-prone spontaneously hypertensive rat (SHRSP). Halothane-anesthetized, 3- to 5-month-old male and female Wistar-Kyoto rats (WKY), SHRSP, and the first filial generation rats (F1 crosses 1 and 2) underwent distal (2 mm) permanent middle cerebral artery occlusion (MCAO) by electrocoagulation. Infarct volume was measured by using hematoxylin-eosin-stained sections and image analysis 24 hours after ischemia and expressed as a percentage of the volume of the ipsilateral hemisphere. Infarct volume in males and females grouped together were significantly larger in SHRSP, F1 cross 1 (SHRSP father), and F1 cross 2 (WKY father), at 36.6+/-2.3% (mean+/-SEM, P<0.001, n=15), 25.4+/-2.4% (P<0.01, n=14), and 33. 9+/-1.6% (P<0.001, n=18), respectively, compared with WKY (14+/-2%, n=17). Male F1 cross 1 (18.9+/-2.4%, n=6) developed significantly smaller infarcts than male F1 cross 2 (32.8+/-2%, n=8, P<0.005). Females, which underwent ischemia during metestrus, developed larger infarcts than respective males. A group of females in which the cycle was not controlled for developed significantly smaller infarcts than females in metestrus. Thus, the increased sensitivity to MCAO in SHRSP is retained in both F1 cross 1 and cross 2 hybrids, suggesting a dominant or codominant trait; response to cerebral ischemia appears to be affected by gender and stage in the estrous cycle. In addition, the male progenitor of the cross (ie, SHRSP versus WKY) influences stroke sensitivity in male F1 cohorts.
我们研究了易患中风的自发性高血压大鼠（SHRSP）对局灶性脑缺血敏感性增加的遗传传递以及性别的影响。对氟烷麻醉的3至5月龄雄性和雌性Wistar-Kyoto大鼠（WKY）、SHRSP以及第一代子代大鼠（F1杂交1和2）进行电凝法造成远端（2毫米）大脑中动脉永久性闭塞（MCAO）。缺血24小时后，使用苏木精-伊红染色切片和图像分析测量梗死体积，并表示为同侧半球体积的百分比。SHRSP、F1杂交1（SHRSP父亲）和F1杂交2（WKY父亲）中，雄性和雌性合并组的梗死体积显著大于WKY，分别为36.6±2.3%（平均值±标准误，P<0.001，n=15）、25.4±2.4%（P<0.01，n=14）和33.9±1.6%（P<0.001，n=18），而WKY为14±2%（n=17）。雄性F1杂交1（18.9±2.4%，n=6）的梗死体积显著小于雄性F1杂交2（32.8±2%，n=8，P<0.005）。处于动情后期缺血的雌性比相应雄性产生更大的梗死体积。一组未控制周期的雌性产生的梗死体积显著小于处于动情后期的雌性。因此，SHRSP对MCAO的敏感性增加在F1杂交1和杂交2杂种中均得以保留，表明这是一种显性或共显性性状；对脑缺血的反应似乎受性别和动情周期阶段的影响。此外，杂交的雄性亲本（即SHRSP与WKY）影响雄性F1群体的中风敏感性。
