Yang Shaolong, Choudhry Mashkoor A, Hsieh Ya-Ching, Hu Shunhua, Rue Loring W, Bland Kirby I, Chaudry Irshad H
Department of Surgery, University of Alabama at Birmingham, AL 35294-0019, USA.
Am J Physiol Heart Circ Physiol. 2006 Dec;291(6):H2807-15. doi: 10.1152/ajpheart.00195.2006. Epub 2006 Jul 28.
Since cardiac function is depressed in males but not in proestrus (PE) females following trauma-hemorrhage (T-H), we examined whether different estrus cycles influence cardiac function in female rats under those conditions. We hypothesized that females in the PE cycle only will have normal cardiac function following T-H and resuscitation. Sham operation or T-H was performed in five groups of rats (250-275 g) including PE, estrus (E), metestrus (ME), diestrus (DE), and ovariectomized (OVX) females (n = 6-7 per group). Cardiac function was determined 2 h after T-H, following which cardiomyocytes were isolated and nuclei extracted. Cardiomyocyte IL-6 and NF-kappaB expressions were measured using Western blotting. Moreover, plasma IL-6, estradiol, and progesterone levels were measured using ELISA or EIA kits. Results (1-way ANOVA) indicated that following T-H, 1) cardiac function was depressed in DE, E, ME, and OVX groups but maintained in the PE group; 2) the PE group had the highest plasma estrogen level; 3) plasma IL-6 levels increased significantly in DE, E, ME, and OVX groups, but the increase was attenuated in the PE group; 4) cardiomyocyte IL-6 protein level increased significantly in DE, E, ME and OVX groups after TH, but the increase was attenuated in the PE group; and 5) cardiomyocyte NF-kappaB expression increased significantly but was attenuated in the PE group. These data collectively suggest that the estrus cycle plays an important role in cardiac function following TH. The salutary effect seen in PE following TH is likely due to a decrease in NF-kappaB-dependent cardiac IL-6 pathway.
由于创伤性出血(T-H)后雄性大鼠的心脏功能受到抑制,而处于动情前期(PE)的雌性大鼠则未受影响,因此我们研究了在这些条件下不同的发情周期是否会影响雌性大鼠的心脏功能。我们假设只有处于PE周期的雌性大鼠在T-H和复苏后心脏功能才会正常。对五组大鼠(体重250 - 275克)进行假手术或T-H,这些大鼠包括处于PE期、发情期(E)、动情后期(ME)、动情间期(DE)的雌性大鼠以及去卵巢(OVX)雌性大鼠(每组n = 6 - 7)。在T-H后2小时测定心脏功能,之后分离心肌细胞并提取细胞核。使用蛋白质免疫印迹法测量心肌细胞白细胞介素-6(IL-6)和核因子κB(NF-κB)的表达。此外,使用酶联免疫吸附测定(ELISA)或酶免疫分析(EIA)试剂盒测量血浆IL-6、雌二醇和孕酮水平。结果(单因素方差分析)表明,T-H后:1)DE、E、ME和OVX组的心脏功能受到抑制,但PE组的心脏功能保持正常;2)PE组的血浆雌激素水平最高;3)DE、E、ME和OVX组的血浆IL-6水平显著升高,但PE组的升高幅度减弱;4)T-H后DE、E、ME和OVX组的心肌细胞IL-6蛋白水平显著升高,但PE组的升高幅度减弱;5)心肌细胞NF-κB表达显著增加,但在PE组中减弱。这些数据共同表明,发情周期在T-H后的心脏功能中起重要作用。T-H后PE组出现的有益作用可能是由于依赖NF-κB的心脏IL-6信号通路的减少。