Wu Huan, Gong Shipeng, Liu Shisan, Yao Suo, Liu Qianqian, Yu Yanhong
Department of Obstetrics and Gynecology, Nanfang Hospital of Southern Medical University, Guangzhou 510515, China.
Department of Obstetrics and Gynecology, Nanfang Hospital of Southern Medical University, Guangzhou 510515, China; Email:
Zhonghua Fu Chan Ke Za Zhi. 2015 Jul;50(7):522-8.
The paper is an attentative effort to evaluate the reaction and mechanism of estrogen on pregnant rabbits with acute lung injury caused by hemorrhagic shock.
Sixty pregnant New Zealand white rabbits were randomly divided into 6 groups, with 10 rabbits in each group, namely normal control group (NG group, with anesthesia only), estrogen group (E(2)G group, with additional estrogen injection at 60 min) and the other four hemorrhagic shock groups underwent hemorrhagic shock (i.e. E(2)SG, FSG, SBSG, E(2)SBSG group; mean blood pressure- 40 mmHg (1 mmHg = 0.133 kPa) by phlebotomy for 15 min. After maintenance of the pressure for 45 min, the rabbits were treated with E(2) (0.37 mg/kg), fructose injection (5%, 2 ml/kg), the p38 mitogen-activated protein kinases (p38MAPK) inhibitor SB-203580 (2 mg/kg) or E(2) plus SB-203580. Tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) were measured at different time points (0 min, 60 min, 80 min and 260 min), lung tissue methane dicarboxylic aldehyde (MDA) level, lung tissue myeloperoxidase (MOP), superoxide dismutase (SOD) activity, lung tissue dry weight/wet weight (DW/WW) value were measured after the experiment was finished, pulmonary pathology of the rabbits was observed.
(1) Serum TNF-α level of NG group and E(2)SG group were not significantly different compared with the other four groups at the 0 min and 60 min. At 80 min and 260 min of experiment, serum TNF-α level of all the four shock groups were increased, E(2)SG group [(172.4 ± 16.0) and (216.7 ± 18.6) ng/L], FSG group [(171.6 ± 9.1) and (263.9 ± 7.8) ng/L], SBSG group [(172.8 ± 7.2) and (300.6 ± 4.8) ng/L], E(2)SBSG group [(167.9 ± 4.8 ) and (261.8 ± 9.6) ng/L], and significantly higher than NG group and E(2)G group, separately (P < 0.05). (2) Serum IL-6 level of NG group and E(2)SG group were not significantly different compared with the other four groups at the 0 min, 60 min and 80 min. At 260 min, the serum IL-6 level [(98.3 ± 0.9) and (110.4 ± 1.8) ng/L; (120.9 ± 2.3) and (109.8 ± 2.6) ng/L] of the four shock groups (E(2)SG, FSG, SBSG, E(2)SBSG group) were significantly higher than NG group and E(2)G group (P < 0.05). (3) Lung tissue MDA level [(2.20 ± 0.12), (2.57 ± 0.11), (3.17 ± 0.08), (2.75 ± 1.09) nmol/mg] and MPO activity [(4.45 ± 0.25), (6.65 ± 0.56), (9.55 ± 0.30), (6.78 ± 0.11) U/mg] of the four shock groups (E(2)SG, FSG, SBSG, E(2)SBSG group) were higher than NG group and E(2)G group (P < 0.05). (4) Lung tissue SOD activity [(51.8 ± 1.8), (40.2 ± 1.5), (30.0 ± 1.7), (41.2 ± 2.0) U/mg] was significantly higher in the four shock groups (E(2)SG, FSG, SBSG, E(2)SBSG group) compared with NG group and E(2)G group (P < 0.05). (5) Lung tissue DW/WW value (0.143 ± 0.008, 0.127 ± 0.008, 0.109 ± 0.006, 0.125 ± 0.008) was significantly lower in the four shock groups (E(2)SG, FSG, SBSG, E(2)SBSG group) compared with NG group and E(2)G group (P < 0.05). (6) Lung tissue of the rabbits in NG group and E(2)G group is basically normal without obvious pathology changes. Lung tissue pathological damage of rabbits was observed in the four shock groups, and the pathological damage of rabbits in SBSG group was most serious.
Estrogen can reduce acute lung injury of pregnant rabbits with hemorrhagic shock, the p38MAPK pathway plays a critical role in mediating the salutary effects of E(2) on shock-induced acute lung injury.
本研究旨在探讨雌激素对失血性休克致孕兔急性肺损伤的反应及作用机制。
将60只孕新西兰白兔随机分为6组，每组10只，即正常对照组（NG组，仅麻醉）、雌激素组（E(2)G组，60 min时额外注射雌激素），另外4个失血性休克组（即E(2)SG、FSG、SBSG、E(2)SBSG组；通过放血15 min使平均血压维持在40 mmHg（1 mmHg = 0.133 kPa）。维持该血压45 min后，对兔分别给予E(2)（0.37 mg/kg）、果糖注射液（5%，2 ml/kg）、p38丝裂原活化蛋白激酶（p38MAPK）抑制剂SB - 203580（2 mg/kg）或E(2)加SB - 203580。于不同时间点（0 min、60 min、80 min和260 min）检测肿瘤坏死因子α（TNF-α）、白细胞介素-6（IL-6），实验结束后检测肺组织丙二醛（MDA）水平、肺组织髓过氧化物酶（MOP）、超氧化物歧化酶（SOD）活性、肺组织干重/湿重（DW/WW）值，观察兔肺组织病理学变化。
（1）0 min和60 min时，NG组和E(2)SG组血清TNF-α水平与其他4组相比差异无统计学意义。实验80 min和260 min时，4个休克组血清TNF-α水平均升高，E(2)SG组[（172.4±16.0）和（216.7±18.6）ng/L]、FSG组[（171.6±9.1）和（263.9±7.8）ng/L]、SBSG组[（172.8±7.2）和（300.6±4.8）ng/L]、E(2)SBSG组[（167.9±4.8）和（261.8±9.6）ng/L]，且分别显著高于NG组和E(2)G组（P < 0.05）。（2）0 min、60 min和80 min时，NG组和E(2)SG组血清IL-6水平与其他4组相比差异无统计学意义。260 min时，4个休克组（E(2)SG、FSG、SBSG、E(2)SBSG组）血清IL-6水平[（98.3±0.9）和（110.4±1.8）ng/L；（120.9±2.3）和（109.8±2.6）ng/L]显著高于NG组和E(2)G组（P < 0.05）。（3）4个休克组（E(2)SG、FSG、SBSG、E(2)SBSG组）肺组织MDA水平[（2.20±0.12）、（2.57±0.11）、（3.17±0.08）、（2.75±1.09）nmol/mg]和MOP活性[（4.45±0.25）、（6.65±0.56）、（9.55±0.30）、（6.78±0.11）U/mg]高于NG组和E(2)G组（P < 0.05）。（4）4个休克组（E(2)SG、FSG、SBSG、E(2)SBSG组）肺组织SOD活性[（51.8±1.8）、（40.2±1.5）、（30.0±1.7）、（41.2±2.0）U/mg]显著高于NG组和E(2)G组（P < 0.05）。（5）4个休克组（E(2)SG、FSG、SBSG、E(2)SBSG组）肺组织DW/WW值（0.143±0.008，0.127±0.008，0.109±0.006，0.125±0.008）显著低于NG组和E(2)G组（P < 0.05）。（6）NG组和E(2)G组兔肺组织基本正常，无明显病理改变。4个休克组均观察到兔肺组织病理损伤，其中SBSG组兔病理损伤最严重。
雌激素可减轻失血性休克孕兔的急性肺损伤，p38MAPK通路在介导E(2)对休克诱导的急性肺损伤的有益作用中起关键作用。
