中华妇产科杂志
中華婦產科雜誌
중화부산과잡지
CHINESE JOUNAL OF OBSTETRICS AND GYNECOLOGY
2015年
7期
522-528
,共7页
吴焕%龚时鹏%刘士三%姚硕%刘倩倩%余艳红
吳煥%龔時鵬%劉士三%姚碩%劉倩倩%餘豔紅
오환%공시붕%류사삼%요석%류천천%여염홍
雌激素类%休克,出血性%急性肺损伤%产后出血%疾病模型,动物
雌激素類%休剋,齣血性%急性肺損傷%產後齣血%疾病模型,動物
자격소류%휴극,출혈성%급성폐손상%산후출혈%질병모형,동물
Estrogens%Shock,hemorrhagic%Acute lung injury%Postpartum hemorrhage%Disease models,animal
目的:探讨雌激素对失血性休克孕兔发生急性肺损伤的影响及其机制。方法60只孕兔随机分为6组,每组10只,正常对照组(无任何处理)、雌激素对照组(静脉注射苯甲酸雌二醇0.37 mg/kg),以下4组孕兔先行休克及复苏处理后再分组处理:雌激素休克组(静脉注射苯甲酸雌二醇0.37 mg/kg)、果糖休克组(静脉注射5%果糖2 ml/kg)、p38丝裂原活化蛋白激酶(p38激酶)抑制剂休克组(静脉注射p38激酶抑制剂2 mg/kg)、p38激酶抑制剂+雌激素休克组(处理同p38激酶抑制剂休克组及雌激素休克组)。各组孕兔分别于实验0、60、80及260 min时,检测血清肿瘤坏死因子α(TNF-α)及白细胞介素6(IL-6)的水平;孕兔处死后行肺组织丙二醛(MDA)含量、髓过氧化物酶(MPO)及超氧化物歧化酶(SOD)活性的检测;计算肺组织的肺干/湿质量(DW/WW)比值;对肺组织进行病理检查。结果(1)正常对照组及雌激素休克组孕兔血清TNF-α水平在实验0 min、60 min时与其他4组比较,差异均无统计学意义(P>0.05)。实验80、260 min时,各休克组孕兔血清TNF-α水平呈上升趋势,雌激素休克组[分别为(172.4±16.0)、(216.7±18.6)ng/L]、果糖休克组[分别为(171.6±9.1)、(263.9±7.8)ng/L]、p38激酶抑制剂休克组[分别为(172.8±7.2)、(300.6±4.8)ng/L]及p38激酶抑制剂+雌激素休克组[分别为(167.9±4.8)、(261.8±9.6)ng/L],分别与正常对照组和雌激素对照组比较,差异均有统计学意义(P<0.05)。(2)正常对照组及雌激素休克组孕兔血清IL-6水平在实验0、60、80 min时分别与其他4组比较,差异均无统计学意义(P>0.05);实验260 min时,雌激素休克组、果糖休克组、p38激酶抑制剂休克组及p38激酶抑制剂+雌激素休克组孕兔血清IL-6水平[分别为(98.3±0.9)、(110.4±1.8)、(120.9±2.3)、(109.8±2.6)ng/L]分别与正常对照组和雌激素对照组比较,差异均有统计学意义(P<0.05)。(3)与正常对照组和雌激素对照组比较,雌激素休克组、果糖休克组、p38激酶抑制剂休克组及p38激酶抑制剂+雌激素休克组孕兔肺组织MDA含量[分别为(2.20±0.12)、(2.57±0.11)、(3.17±0.08)、(2.75±1.09)nmol/mg]及MPO活性水平[分别为(4.45±0.25)、(6.65±0.56)、(9.55±0.30)、(6.78±0.11)U/mg]均明显升高,分别比较,差异均有统计学意义(P<0.05)。(4)与正常对照组和雌激素对照组比较,雌激素休克组、果糖休克组、p38激酶抑制剂休克组及p38激酶抑制剂+雌激素休克组孕兔肺组织SOD活性水平均明显降低[分别为(51.8±1.8)、(40.2±1.5)、(30.0±1.7)、(41.2±2.0)U/mg],分别比较,差异均有统计学意义(P<0.05)。(5)与正常对照组和雌激素对照组比较,雌激素休克组、果糖休克组、p38激酶抑制剂休克组及p38激酶抑制剂+雌激素休克组孕兔肺组织DW/WW比值明显降低(分别为0.143±0.008、0.127±0.008、0.109±0.006、0.125±0.008),分别比较,差异均有统计学意义(P<0.05)。(6)正常对照组和雌激素对照组孕兔肺组织未见明显病理变化;雌激素休克组、果糖休克组、p38激酶抑制剂休克组及p38激酶抑制剂+雌激素休克组孕兔肺组织均出现损伤性病理改变,p38激酶抑制剂休克组孕兔肺组织损伤程度最为严重。结论雌激素可以在一定程度上保护失血性休克孕兔的急性肺损伤发生,其保护作用机制可能主要是通过p38激酶途径而实现。
目的:探討雌激素對失血性休剋孕兔髮生急性肺損傷的影響及其機製。方法60隻孕兔隨機分為6組,每組10隻,正常對照組(無任何處理)、雌激素對照組(靜脈註射苯甲痠雌二醇0.37 mg/kg),以下4組孕兔先行休剋及複囌處理後再分組處理:雌激素休剋組(靜脈註射苯甲痠雌二醇0.37 mg/kg)、果糖休剋組(靜脈註射5%果糖2 ml/kg)、p38絲裂原活化蛋白激酶(p38激酶)抑製劑休剋組(靜脈註射p38激酶抑製劑2 mg/kg)、p38激酶抑製劑+雌激素休剋組(處理同p38激酶抑製劑休剋組及雌激素休剋組)。各組孕兔分彆于實驗0、60、80及260 min時,檢測血清腫瘤壞死因子α(TNF-α)及白細胞介素6(IL-6)的水平;孕兔處死後行肺組織丙二醛(MDA)含量、髓過氧化物酶(MPO)及超氧化物歧化酶(SOD)活性的檢測;計算肺組織的肺榦/濕質量(DW/WW)比值;對肺組織進行病理檢查。結果(1)正常對照組及雌激素休剋組孕兔血清TNF-α水平在實驗0 min、60 min時與其他4組比較,差異均無統計學意義(P>0.05)。實驗80、260 min時,各休剋組孕兔血清TNF-α水平呈上升趨勢,雌激素休剋組[分彆為(172.4±16.0)、(216.7±18.6)ng/L]、果糖休剋組[分彆為(171.6±9.1)、(263.9±7.8)ng/L]、p38激酶抑製劑休剋組[分彆為(172.8±7.2)、(300.6±4.8)ng/L]及p38激酶抑製劑+雌激素休剋組[分彆為(167.9±4.8)、(261.8±9.6)ng/L],分彆與正常對照組和雌激素對照組比較,差異均有統計學意義(P<0.05)。(2)正常對照組及雌激素休剋組孕兔血清IL-6水平在實驗0、60、80 min時分彆與其他4組比較,差異均無統計學意義(P>0.05);實驗260 min時,雌激素休剋組、果糖休剋組、p38激酶抑製劑休剋組及p38激酶抑製劑+雌激素休剋組孕兔血清IL-6水平[分彆為(98.3±0.9)、(110.4±1.8)、(120.9±2.3)、(109.8±2.6)ng/L]分彆與正常對照組和雌激素對照組比較,差異均有統計學意義(P<0.05)。(3)與正常對照組和雌激素對照組比較,雌激素休剋組、果糖休剋組、p38激酶抑製劑休剋組及p38激酶抑製劑+雌激素休剋組孕兔肺組織MDA含量[分彆為(2.20±0.12)、(2.57±0.11)、(3.17±0.08)、(2.75±1.09)nmol/mg]及MPO活性水平[分彆為(4.45±0.25)、(6.65±0.56)、(9.55±0.30)、(6.78±0.11)U/mg]均明顯升高,分彆比較,差異均有統計學意義(P<0.05)。(4)與正常對照組和雌激素對照組比較,雌激素休剋組、果糖休剋組、p38激酶抑製劑休剋組及p38激酶抑製劑+雌激素休剋組孕兔肺組織SOD活性水平均明顯降低[分彆為(51.8±1.8)、(40.2±1.5)、(30.0±1.7)、(41.2±2.0)U/mg],分彆比較,差異均有統計學意義(P<0.05)。(5)與正常對照組和雌激素對照組比較,雌激素休剋組、果糖休剋組、p38激酶抑製劑休剋組及p38激酶抑製劑+雌激素休剋組孕兔肺組織DW/WW比值明顯降低(分彆為0.143±0.008、0.127±0.008、0.109±0.006、0.125±0.008),分彆比較,差異均有統計學意義(P<0.05)。(6)正常對照組和雌激素對照組孕兔肺組織未見明顯病理變化;雌激素休剋組、果糖休剋組、p38激酶抑製劑休剋組及p38激酶抑製劑+雌激素休剋組孕兔肺組織均齣現損傷性病理改變,p38激酶抑製劑休剋組孕兔肺組織損傷程度最為嚴重。結論雌激素可以在一定程度上保護失血性休剋孕兔的急性肺損傷髮生,其保護作用機製可能主要是通過p38激酶途徑而實現。
목적:탐토자격소대실혈성휴극잉토발생급성폐손상적영향급기궤제。방법60지잉토수궤분위6조,매조10지,정상대조조(무임하처리)、자격소대조조(정맥주사분갑산자이순0.37 mg/kg),이하4조잉토선행휴극급복소처리후재분조처리:자격소휴극조(정맥주사분갑산자이순0.37 mg/kg)、과당휴극조(정맥주사5%과당2 ml/kg)、p38사렬원활화단백격매(p38격매)억제제휴극조(정맥주사p38격매억제제2 mg/kg)、p38격매억제제+자격소휴극조(처리동p38격매억제제휴극조급자격소휴극조)。각조잉토분별우실험0、60、80급260 min시,검측혈청종류배사인자α(TNF-α)급백세포개소6(IL-6)적수평;잉토처사후행폐조직병이철(MDA)함량、수과양화물매(MPO)급초양화물기화매(SOD)활성적검측;계산폐조직적폐간/습질량(DW/WW)비치;대폐조직진행병리검사。결과(1)정상대조조급자격소휴극조잉토혈청TNF-α수평재실험0 min、60 min시여기타4조비교,차이균무통계학의의(P>0.05)。실험80、260 min시,각휴극조잉토혈청TNF-α수평정상승추세,자격소휴극조[분별위(172.4±16.0)、(216.7±18.6)ng/L]、과당휴극조[분별위(171.6±9.1)、(263.9±7.8)ng/L]、p38격매억제제휴극조[분별위(172.8±7.2)、(300.6±4.8)ng/L]급p38격매억제제+자격소휴극조[분별위(167.9±4.8)、(261.8±9.6)ng/L],분별여정상대조조화자격소대조조비교,차이균유통계학의의(P<0.05)。(2)정상대조조급자격소휴극조잉토혈청IL-6수평재실험0、60、80 min시분별여기타4조비교,차이균무통계학의의(P>0.05);실험260 min시,자격소휴극조、과당휴극조、p38격매억제제휴극조급p38격매억제제+자격소휴극조잉토혈청IL-6수평[분별위(98.3±0.9)、(110.4±1.8)、(120.9±2.3)、(109.8±2.6)ng/L]분별여정상대조조화자격소대조조비교,차이균유통계학의의(P<0.05)。(3)여정상대조조화자격소대조조비교,자격소휴극조、과당휴극조、p38격매억제제휴극조급p38격매억제제+자격소휴극조잉토폐조직MDA함량[분별위(2.20±0.12)、(2.57±0.11)、(3.17±0.08)、(2.75±1.09)nmol/mg]급MPO활성수평[분별위(4.45±0.25)、(6.65±0.56)、(9.55±0.30)、(6.78±0.11)U/mg]균명현승고,분별비교,차이균유통계학의의(P<0.05)。(4)여정상대조조화자격소대조조비교,자격소휴극조、과당휴극조、p38격매억제제휴극조급p38격매억제제+자격소휴극조잉토폐조직SOD활성수평균명현강저[분별위(51.8±1.8)、(40.2±1.5)、(30.0±1.7)、(41.2±2.0)U/mg],분별비교,차이균유통계학의의(P<0.05)。(5)여정상대조조화자격소대조조비교,자격소휴극조、과당휴극조、p38격매억제제휴극조급p38격매억제제+자격소휴극조잉토폐조직DW/WW비치명현강저(분별위0.143±0.008、0.127±0.008、0.109±0.006、0.125±0.008),분별비교,차이균유통계학의의(P<0.05)。(6)정상대조조화자격소대조조잉토폐조직미견명현병리변화;자격소휴극조、과당휴극조、p38격매억제제휴극조급p38격매억제제+자격소휴극조잉토폐조직균출현손상성병리개변,p38격매억제제휴극조잉토폐조직손상정도최위엄중。결론자격소가이재일정정도상보호실혈성휴극잉토적급성폐손상발생,기보호작용궤제가능주요시통과p38격매도경이실현。
Objective 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. Methods 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 (E2G group, with additional estrogen injection at 60 min) and the other four hemorrhagic shock groups underwent hemorrhagic shock (i.e. E2SG, FSG, SBSG, E2SBSG 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 E2(0.37 mg/kg), fructose injection(5%,2 ml/kg), the p38 mitogen-activated protein kinases(p38MAPK) inhibitor SB-203580 (2 mg/kg) or E2 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. Result (1) Serum TNF-α level of NG group and E2SG 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-αlevel of all the four shock groups were increased, E2SG 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], E2SBSG group [(167.9±4.8 )and (261.8±9.6) ng/L], and significantly higher than NG group and E2G group, separately (P<0.05). (2) Serum IL-6 level of NG group and E2SG 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 (E2SG, FSG, SBSG, E2SBSG group) were significantly higher than NG group and E2G 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 (E2SG, FSG, SBSG, E2SBSG group) were higher than NG group and E2G 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(E2SG, FSG, SBSG, E2SBSG group) compared with NG group and E2G 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(E2SG, FSG, SBSG, E2SBSG group) compared with NG group and E2G group (P<0.05). (6) Lung tissue of the rabbits in NG group and E2G 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. Conclusion 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 E2 on shock-induced acute lung injury.