内皮素-1、血管内皮生长因子、缺氧诱导因子-1在新生鼠肺出血发生中的作用
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摘要
第一部分
低温缺氧/复温供氧新生鼠肺出血模型的分段建立
目的分段建立低温缺氧/复温供氧新生鼠肺出血模型,探讨新生鼠在缺氧、低温缺氧、低温缺氧后常氧复温、低温缺氧后高氧复温等不同影响因素作用下肺大体和组织学的改变;
方法选用出生后7～8天的Wister新生鼠58只,随机分为正常组(C组)10只,缺氧组(H组),低温缺氧组(HH组),低温缺氧后常氧复温组(HHR)和低温缺氧后高氧复温组(HHRO_2组)各12只。C组置常温室内,H组予缺氧(FiO_25～6%)6h,HH组缺氧同时置10±1℃冷室内,予低温缺氧6h,HHR组同HH组进行低温缺氧6h,然后置37℃环境复温并吸入空气(常氧)2h,HHRO_2组同HHR组,但复温时供高浓度氧(FiO_2＞95%)。各组新生鼠处死后取肺组织,观察肺大体情况,切片HE染色观察肺组织病理学改变。肺大体改变按等级不同分为5级。
结果1.实验组新生鼠共死亡13只,死亡率27.08%(13/48),C组无死亡;2.H组、HH组、HHR组和HHRO_2组肺大体均有改变,H组呈现水肿,HH瘀血明显,可见点状和局灶性出血,HHR组和HHRO_2组见局灶出血增多,HHR组有2例弥漫性出血,HHRO_2组有4例呈弥漫性出血,弥漫性肺出血主要发生在复温复氧阶段;各实验组肺大体改变与C组比较均有显著性差异;组间比较除HHR组与HHRO_2组外,其余各组间比较均有显著性差异。3.各实验组组织学改变包括肺泡及间质水肿、肺间隔断裂、肺泡扩张及融合和肺泡出血。
结论低温缺氧/复温供氧能成功诱发新生鼠肺出血,肺出血发生由肺水肿向点状肺出血、局灶肺出血、弥漫性肺出血发展,弥漫性肺出血主要发生在复温供氧后;缺氧、低温缺氧及复温供氧各阶段均对肺组织造成损伤;高浓度氧可能造成更严重损伤。
第二部分
内皮素-1、血管内皮生长因子、缺氧诱导因子-1在新生鼠肺出血发生过程中肺内的表达
目的探讨在低温缺氧/复温供氧新生鼠肺出血过程中内皮素-1(ET-1)、血管内皮生长因子(VEGF)、缺氧诱导因子-1(HIF-1)在肺组织中的表达与作用。
方法选用出生后7～8天的Wister新生鼠58只,随机分为正常组(C组)10只,缺氧组(H组),低温缺氧组(HH组),低温缺氧后常氧复温组(HHR)和低温缺氧后高氧复温组(HHRO_2组)各12只,模型分段复制过程同第一部分。分别采用逆转录-聚合酶链反应(RT-PCR)方法检测肺组织中前内皮素原mRNA(ppET-1mRNA)、VEGFmRNA、缺氧诱导因子-1αmRNA(HIF-1αmRNA)的表达;放射免疫方法检测肺组织中ET-1含量;WesternBlot方法和免疫组化方法检测VEGF在肺组织中的表达。
结果1.ppET-1mRNA在H组、HH组、HHRO_2组表达增强,与C组比较,P均<0.01;ET-1含量在各实验组均增高,进入复温供氧期后有所下降,各组与C组比较P均<0.01;在H组、HH组,ppET-1mRNA表达与肺组织中ET-1含量呈正相关,分别r=0.72和r=0.67,P均<0.05。2.VEGF188mRNA在H组、HH组表达增强,与C组比较,P均<0.01;VEGF蛋白在各实验组表达增强,与C组比较,H组、HH组P均<0.05,HHR组和HHRO_2组P均<0.01。3.在H、HH组,ET-1与VEGF表达成正相关,分别r=0.72和r=0.66,P均<0.05;4.HIF-1αmRNA表达在各组中无显著性差异,P>0.05。
结论1.ET-1和VEGF在各个阶段都参与肺出血的形成;2.ET-1可能促进了VEGF的表达;3.HIF-1α在肺出血中作为核转录因子参与调控ET-1和VEGF的表达,但低氧对其调控主要在转录后水平。
第三部分内皮素-1双重受体阻断剂对新生鼠肺出血的预防作用
目的观察ET-1双重受体阻断剂(波生坦)能否降低低温缺氧/复温供氧新生鼠肺出血发生率以及肺组织中VEGF的表达,评价波生坦在预防肺出血发生中的作用。
方法选用出生后7～8天的Wister新生鼠106只,随机分为正常组(C组)10只,实验组和波生坦组各48只;实验组和波生坦组再分为H、HH、HHR、HHRO_24个亚组各12只,波生坦组实验前2h经胃管灌注波生坦,模型分步复制过程同第一部分。观察各组肺大体改变,采用Western Blot方法检测VEGF在肺组织中的表达。
结果1.波生坦组新生鼠死亡5只,实验组死亡13只,两组死亡率比较有显著性差异,X~2=3.35,P＜0.05;2.实验组肺大体改变同第一部分,包括水肿、点状出血、局灶性出血甚至弥漫性出血,波生坦组中各亚组肺大体改变均较实验组有所减轻,从HH亚组开始仍见点状肺出血发生,HHR和HHRO_2亚组可见局灶性出血,但未出现弥漫性出血,HHR和HHRO_2亚组肺大体改变与实验组相应亚组比较有显著性差异,分别T=193.5,P＜0.05和T=199.0,P＜0.01;3.与正常组比较,波生坦组中各亚组VEGF表达无显著性差异,H=3.43,P＞0.05。
结论ET-1受体阻断剂能减轻新生鼠低温缺氧/复温供氧肺出血的发生,其机制与阻断ET-1的作用及下调VEGF表达有关。
Part 1
The establishment of pulmonary hemorrhage model in different phases in newborn rats induced by hypothermia-hypoxia/rewarming-reoxygenating
Objective To establish pulmonary hemorrhage model in different phases in newborn rats induced by hypothermia-hypoxia/rewarming- reoxygenating and to investigate the gross anatomical and histological changes in lungs under different conditions of hypoxia,hypothermia- hypoxia,hypothermia-hypoxia/ rewarming-reoxygenating with normoxia and hypothermia-hypoxia/rewarmingreoxygenating with hyperoxia.
Methords 58 Wister newborn rats were randomly divided into 5 groups: control group(group C,n=10)and four experimental groups:group H(n=12), group HH(n=12),group HHR(n=12),group HHRO_2(n=12).Group C were exposed to normothermia and normoxia and,group H to hypoxia(5～6%O_2) for 6 hours,group HH to hypothermia(10±1℃)and hypoxia for 6 hours,group HHR to hypothermia and hypoxia for 6 hours and then to hyperthermia(37℃) and normoxia for 2 hours,group HHRO_2 to hypothermia and hypoxia for 6 hours and then to hyperthermia and hyperoxia(＞95%O_2)for 2 hours.The gross anatomical and histological changes(HE staining)in lungs were observed.There were 5 degrees in the changes of gross anatomical in lungs.
Results(1)13 rats in experimental groups died while none in group C and the mortality rate of experimental groups was 27.08%.(2)Lungs of group H represented edema and,markedly stagnated blood,spotty pulmonary hemorrhage,local pulmonary hemorrhage could be observed in group HH and,more severe pulmonary hemorrhage were observed in groups HHR and HHRO_2,in which 2 cases of group HHR and 4 cases of group HHRO_2 suffered diffuse pulmonary hemorrhage and diffuse pulmonary hemorrhage occured mostly in the phase of rewarming/reoxygenating.There were significan differences of gross anatomical changes between group C and every experimental group and there were significant differences between every two experimental groups except for groups HHR and HHRO_2.(3)Histological changes in experimental groups included pulmonary alveoli and interstitial edema,spacer breaking,pulmonary alveoli dilating,fusion and pulmonary alveoli hemorrhage.
Conclusion Pulmonary hemorrahge model can be established successfully in new born rats subjected hypothermia-hypoxia/rewarming -reoxygenating.Pulmonary hemorrhage developed from pulmonary edema to spotty pulmonary hemorrhage,local pulmonary hemorrhage and diffuse pulmonary hemorrhage.Diffuse pulmonary hemorrhage occured mostly in the phase of rewarming/reoxygenating.Hypoxia,hypothermia-hypoxia and rewarming/reoxygenating are factors contributing to lung injury.Hyperoxia may induce more severe lung injury.
Part 2
Expressions of endothelin-1,vascular endothelial growth factor, hypoxia inducible factor-1 in pulmonary tissue of newborn rats developing pulmonary hemorrhage
Objective To investigate the expressions and effects of endothelin-1 (ET-1),vascular endothelial growth factor(VEGF),hypoxia inducible factor-1 (HIF-1)in pulmonary tissue of newborn rats developing pulmonary hemorrhage
Methods 58 Wister newborn rats were randomly divided into 5 groups: control group(group C,n=10)and four experimental groups:group H(n=12), group HH(n=12),group HHR(n=12),group HHRO_2(n=12).Pulmonary hemorrhage models were established in different phases as described in part
1.Expressions of preproendothelin-1mRNA(ppET-1mRAN),VEGFmRNA, HIF-1αmRNA were studied by reverse transcription-polymerase chain reaction (RT-PCR).Contents of ET-1 in pulmonary tissues were measured by radioimmunoassay.Expressions of VEGF were studied by Western Blot and immunohistochemical method.
Results(1)Expressions of ppET-1mRAN increased significantly in groups H,HH and HHRO_2(P＜0.01)and contents of ET-1 elevated significantly in all experimental groups especially in groups H and HH(P＜0.01).There were significant positive correlations between the expressions of ppET-1mRAN and contents of ET-1 in groups H and HH(r=0.72,P＜0.05 and r=0.67,P＜0.05, respectively).(2)Expressions of VEGF188mRNA increased significantly in groups H,HH(P＜0.01)while VEGF increased significantly in all experimental groups especially in groups HR and HHRO_2(P＜0.05 in groups H and HH,P＜0.01 in groups HHR and HHRO_2).(3)There were significant positive correlations between the expressions of ET-1 and VEGF in groups H and HH (r=0.72,P＜0.05 and r=0.66,P＜0.05,respectively).(4)There was no significant difference in expressions of HIF-1αmRNA between group C and experimental groups.
Conclusion(1)ET-1 and VEGF may contribute to the development of pulmonary hemorrhage in every phase.(2)ET-1 may promote the expression of VEGF.(3)HIF-1,as a transcription factor,may participate the pathological process by regulates the expressions of ET-1 and VEGF.Hypoxia regulates the expression of HIF-1αby a post-transcriptional mechanism.
Part 3
Effect of dual endothelin-1 receptor antagonist on prevention of pulmonary hemorrhage in newborn rats
Objective To study if dual endothelin-1 receptor antagonist,bosentan,can decrease the incidence of pulmonary hemorrhage in newborn rats induced by hypothermia-hypoxia/rewarming-reoxygenating and alter the expression of VEGF in pulmonary tissue and to evaluate the effect of bosentan on prevention of pulmonary hemorrhage.
Methods 106 Wister newborn rats were randomly divided into 3 groups: control group(group C,n=10),experimental group(n=48)and bosantan group (n=48).Pups in experimental and bosentan groups were randomly divided into four subgroup:subgroup H(n=12),subgroup HH(n=12),subgroup HHR(n=12), subgroup HHRO_2(n=12).Rats in bosentan group accepted intragastric administration with bosentan(150mg/kg).2 hours later,the pulmonary hemorrahge models were established in experimental group and bosentan group as described in part 1.The gross anatomical changes in lungs were observed and the expressions of VEGF were studied by Western Blot method.
Results(1)5 rats died in bosentan group while 13 in experimental group.There was a significant difference of mortality rate between experimental group and bosentan group(X~2=3.35,P＜0.05).(2)Gross anatomical findings in experimental groups including edema and pulmonary hemorrhage as described in part 1.Attenuated gross anatomical changes could be observed in bosentan group:spotty pulmonary hemorrhage in subgroup HH and local pulmonary hemorrhage in subgroup HHR and subgroup HHR0_2 could be found,no diffuse pulmonary hemorrhage could be found in any subgroup.There were significant differences of gross anatomical changes between subgroups HHR,HHR0_2 in experimental group and their match subgroups in bosentan group(P＜0.05 and P＜0.01,respectively).(3)There was no significant difference of VEGF expression between group C and bosentant group(P＞0.05).
Conclusion Dual endothelin-1 receptor antagonist,bosentan,can attenuate the pulmonary hemorrhage in newborn rats induced by hypothermia-hypoxia/ rewarming-reoxygenating and the mechanism may correlate with ET-1 blockade and downregulation of the expression of VEFG.
低温缺氧/复温供氧新生鼠肺出血模型的分段建立
目的分段建立低温缺氧/复温供氧新生鼠肺出血模型,探讨新生鼠在缺氧、低温缺氧、低温缺氧后常氧复温、低温缺氧后高氧复温等不同影响因素作用下肺大体和组织学的改变;
方法选用出生后7～8天的Wister新生鼠58只,随机分为正常组(C组)10只,缺氧组(H组),低温缺氧组(HH组),低温缺氧后常氧复温组(HHR)和低温缺氧后高氧复温组(HHRO_2组)各12只。C组置常温室内,H组予缺氧(FiO_25～6%)6h,HH组缺氧同时置10±1℃冷室内,予低温缺氧6h,HHR组同HH组进行低温缺氧6h,然后置37℃环境复温并吸入空气(常氧)2h,HHRO_2组同HHR组,但复温时供高浓度氧(FiO_2＞95%)。各组新生鼠处死后取肺组织,观察肺大体情况,切片HE染色观察肺组织病理学改变。肺大体改变按等级不同分为5级。
结果1.实验组新生鼠共死亡13只,死亡率27.08%(13/48),C组无死亡;2.H组、HH组、HHR组和HHRO_2组肺大体均有改变,H组呈现水肿,HH瘀血明显,可见点状和局灶性出血,HHR组和HHRO_2组见局灶出血增多,HHR组有2例弥漫性出血,HHRO_2组有4例呈弥漫性出血,弥漫性肺出血主要发生在复温复氧阶段;各实验组肺大体改变与C组比较均有显著性差异;组间比较除HHR组与HHRO_2组外,其余各组间比较均有显著性差异。3.各实验组组织学改变包括肺泡及间质水肿、肺间隔断裂、肺泡扩张及融合和肺泡出血。
结论低温缺氧/复温供氧能成功诱发新生鼠肺出血,肺出血发生由肺水肿向点状肺出血、局灶肺出血、弥漫性肺出血发展,弥漫性肺出血主要发生在复温供氧后;缺氧、低温缺氧及复温供氧各阶段均对肺组织造成损伤;高浓度氧可能造成更严重损伤。
第二部分
内皮素-1、血管内皮生长因子、缺氧诱导因子-1在新生鼠肺出血发生过程中肺内的表达
目的探讨在低温缺氧/复温供氧新生鼠肺出血过程中内皮素-1(ET-1)、血管内皮生长因子(VEGF)、缺氧诱导因子-1(HIF-1)在肺组织中的表达与作用。
方法选用出生后7～8天的Wister新生鼠58只,随机分为正常组(C组)10只,缺氧组(H组),低温缺氧组(HH组),低温缺氧后常氧复温组(HHR)和低温缺氧后高氧复温组(HHRO_2组)各12只,模型分段复制过程同第一部分。分别采用逆转录-聚合酶链反应(RT-PCR)方法检测肺组织中前内皮素原mRNA(ppET-1mRNA)、VEGFmRNA、缺氧诱导因子-1αmRNA(HIF-1αmRNA)的表达;放射免疫方法检测肺组织中ET-1含量;WesternBlot方法和免疫组化方法检测VEGF在肺组织中的表达。
结果1.ppET-1mRNA在H组、HH组、HHRO_2组表达增强,与C组比较,P均<0.01;ET-1含量在各实验组均增高,进入复温供氧期后有所下降,各组与C组比较P均<0.01;在H组、HH组,ppET-1mRNA表达与肺组织中ET-1含量呈正相关,分别r=0.72和r=0.67,P均<0.05。2.VEGF188mRNA在H组、HH组表达增强,与C组比较,P均<0.01;VEGF蛋白在各实验组表达增强,与C组比较,H组、HH组P均<0.05,HHR组和HHRO_2组P均<0.01。3.在H、HH组,ET-1与VEGF表达成正相关,分别r=0.72和r=0.66,P均<0.05;4.HIF-1αmRNA表达在各组中无显著性差异,P>0.05。
结论1.ET-1和VEGF在各个阶段都参与肺出血的形成;2.ET-1可能促进了VEGF的表达;3.HIF-1α在肺出血中作为核转录因子参与调控ET-1和VEGF的表达,但低氧对其调控主要在转录后水平。
第三部分内皮素-1双重受体阻断剂对新生鼠肺出血的预防作用
目的观察ET-1双重受体阻断剂(波生坦)能否降低低温缺氧/复温供氧新生鼠肺出血发生率以及肺组织中VEGF的表达,评价波生坦在预防肺出血发生中的作用。
方法选用出生后7～8天的Wister新生鼠106只,随机分为正常组(C组)10只,实验组和波生坦组各48只;实验组和波生坦组再分为H、HH、HHR、HHRO_24个亚组各12只,波生坦组实验前2h经胃管灌注波生坦,模型分步复制过程同第一部分。观察各组肺大体改变,采用Western Blot方法检测VEGF在肺组织中的表达。
结果1.波生坦组新生鼠死亡5只,实验组死亡13只,两组死亡率比较有显著性差异,X~2=3.35,P＜0.05;2.实验组肺大体改变同第一部分,包括水肿、点状出血、局灶性出血甚至弥漫性出血,波生坦组中各亚组肺大体改变均较实验组有所减轻,从HH亚组开始仍见点状肺出血发生,HHR和HHRO_2亚组可见局灶性出血,但未出现弥漫性出血,HHR和HHRO_2亚组肺大体改变与实验组相应亚组比较有显著性差异,分别T=193.5,P＜0.05和T=199.0,P＜0.01;3.与正常组比较,波生坦组中各亚组VEGF表达无显著性差异,H=3.43,P＞0.05。
结论ET-1受体阻断剂能减轻新生鼠低温缺氧/复温供氧肺出血的发生,其机制与阻断ET-1的作用及下调VEGF表达有关。
Part 1
The establishment of pulmonary hemorrhage model in different phases in newborn rats induced by hypothermia-hypoxia/rewarming-reoxygenating
Objective To establish pulmonary hemorrhage model in different phases in newborn rats induced by hypothermia-hypoxia/rewarming- reoxygenating and to investigate the gross anatomical and histological changes in lungs under different conditions of hypoxia,hypothermia- hypoxia,hypothermia-hypoxia/ rewarming-reoxygenating with normoxia and hypothermia-hypoxia/rewarmingreoxygenating with hyperoxia.
Methords 58 Wister newborn rats were randomly divided into 5 groups: control group(group C,n=10)and four experimental groups:group H(n=12), group HH(n=12),group HHR(n=12),group HHRO_2(n=12).Group C were exposed to normothermia and normoxia and,group H to hypoxia(5～6%O_2) for 6 hours,group HH to hypothermia(10±1℃)and hypoxia for 6 hours,group HHR to hypothermia and hypoxia for 6 hours and then to hyperthermia(37℃) and normoxia for 2 hours,group HHRO_2 to hypothermia and hypoxia for 6 hours and then to hyperthermia and hyperoxia(＞95%O_2)for 2 hours.The gross anatomical and histological changes(HE staining)in lungs were observed.There were 5 degrees in the changes of gross anatomical in lungs.
Results(1)13 rats in experimental groups died while none in group C and the mortality rate of experimental groups was 27.08%.(2)Lungs of group H represented edema and,markedly stagnated blood,spotty pulmonary hemorrhage,local pulmonary hemorrhage could be observed in group HH and,more severe pulmonary hemorrhage were observed in groups HHR and HHRO_2,in which 2 cases of group HHR and 4 cases of group HHRO_2 suffered diffuse pulmonary hemorrhage and diffuse pulmonary hemorrhage occured mostly in the phase of rewarming/reoxygenating.There were significan differences of gross anatomical changes between group C and every experimental group and there were significant differences between every two experimental groups except for groups HHR and HHRO_2.(3)Histological changes in experimental groups included pulmonary alveoli and interstitial edema,spacer breaking,pulmonary alveoli dilating,fusion and pulmonary alveoli hemorrhage.
Conclusion Pulmonary hemorrahge model can be established successfully in new born rats subjected hypothermia-hypoxia/rewarming -reoxygenating.Pulmonary hemorrhage developed from pulmonary edema to spotty pulmonary hemorrhage,local pulmonary hemorrhage and diffuse pulmonary hemorrhage.Diffuse pulmonary hemorrhage occured mostly in the phase of rewarming/reoxygenating.Hypoxia,hypothermia-hypoxia and rewarming/reoxygenating are factors contributing to lung injury.Hyperoxia may induce more severe lung injury.
Part 2
Expressions of endothelin-1,vascular endothelial growth factor, hypoxia inducible factor-1 in pulmonary tissue of newborn rats developing pulmonary hemorrhage
Objective To investigate the expressions and effects of endothelin-1 (ET-1),vascular endothelial growth factor(VEGF),hypoxia inducible factor-1 (HIF-1)in pulmonary tissue of newborn rats developing pulmonary hemorrhage
Methods 58 Wister newborn rats were randomly divided into 5 groups: control group(group C,n=10)and four experimental groups:group H(n=12), group HH(n=12),group HHR(n=12),group HHRO_2(n=12).Pulmonary hemorrhage models were established in different phases as described in part
1.Expressions of preproendothelin-1mRNA(ppET-1mRAN),VEGFmRNA, HIF-1αmRNA were studied by reverse transcription-polymerase chain reaction (RT-PCR).Contents of ET-1 in pulmonary tissues were measured by radioimmunoassay.Expressions of VEGF were studied by Western Blot and immunohistochemical method.
Results(1)Expressions of ppET-1mRAN increased significantly in groups H,HH and HHRO_2(P＜0.01)and contents of ET-1 elevated significantly in all experimental groups especially in groups H and HH(P＜0.01).There were significant positive correlations between the expressions of ppET-1mRAN and contents of ET-1 in groups H and HH(r=0.72,P＜0.05 and r=0.67,P＜0.05, respectively).(2)Expressions of VEGF188mRNA increased significantly in groups H,HH(P＜0.01)while VEGF increased significantly in all experimental groups especially in groups HR and HHRO_2(P＜0.05 in groups H and HH,P＜0.01 in groups HHR and HHRO_2).(3)There were significant positive correlations between the expressions of ET-1 and VEGF in groups H and HH (r=0.72,P＜0.05 and r=0.66,P＜0.05,respectively).(4)There was no significant difference in expressions of HIF-1αmRNA between group C and experimental groups.
Conclusion(1)ET-1 and VEGF may contribute to the development of pulmonary hemorrhage in every phase.(2)ET-1 may promote the expression of VEGF.(3)HIF-1,as a transcription factor,may participate the pathological process by regulates the expressions of ET-1 and VEGF.Hypoxia regulates the expression of HIF-1αby a post-transcriptional mechanism.
Part 3
Effect of dual endothelin-1 receptor antagonist on prevention of pulmonary hemorrhage in newborn rats
Objective To study if dual endothelin-1 receptor antagonist,bosentan,can decrease the incidence of pulmonary hemorrhage in newborn rats induced by hypothermia-hypoxia/rewarming-reoxygenating and alter the expression of VEGF in pulmonary tissue and to evaluate the effect of bosentan on prevention of pulmonary hemorrhage.
Methods 106 Wister newborn rats were randomly divided into 3 groups: control group(group C,n=10),experimental group(n=48)and bosantan group (n=48).Pups in experimental and bosentan groups were randomly divided into four subgroup:subgroup H(n=12),subgroup HH(n=12),subgroup HHR(n=12), subgroup HHRO_2(n=12).Rats in bosentan group accepted intragastric administration with bosentan(150mg/kg).2 hours later,the pulmonary hemorrahge models were established in experimental group and bosentan group as described in part 1.The gross anatomical changes in lungs were observed and the expressions of VEGF were studied by Western Blot method.
Results(1)5 rats died in bosentan group while 13 in experimental group.There was a significant difference of mortality rate between experimental group and bosentan group(X~2=3.35,P＜0.05).(2)Gross anatomical findings in experimental groups including edema and pulmonary hemorrhage as described in part 1.Attenuated gross anatomical changes could be observed in bosentan group:spotty pulmonary hemorrhage in subgroup HH and local pulmonary hemorrhage in subgroup HHR and subgroup HHR0_2 could be found,no diffuse pulmonary hemorrhage could be found in any subgroup.There were significant differences of gross anatomical changes between subgroups HHR,HHR0_2 in experimental group and their match subgroups in bosentan group(P＜0.05 and P＜0.01,respectively).(3)There was no significant difference of VEGF expression between group C and bosentant group(P＞0.05).
Conclusion Dual endothelin-1 receptor antagonist,bosentan,can attenuate the pulmonary hemorrhage in newborn rats induced by hypothermia-hypoxia/ rewarming-reoxygenating and the mechanism may correlate with ET-1 blockade and downregulation of the expression of VEFG.
引文
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