中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2012年
48期
3429-3433
,共5页
薛熠%代华平%崔瑷%牛淑洁%庞宝森
薛熠%代華平%崔璦%牛淑潔%龐寶森
설습%대화평%최애%우숙길%방보삼
纤溶酶%肺纤维化%博来霉素%大鼠
纖溶酶%肺纖維化%博來黴素%大鼠
섬용매%폐섬유화%박래매소%대서
Plasmin%Pulmonary fibrosis%Bleomycin%Rats
目的 观察蚓激酶雾化吸入是否减轻博来霉素诱发的大鼠肺纤维化及其机制.方法 健康雄性SD大鼠72只,随机分为对照组、博来霉素组、蚓激酶组.博来霉素组和蚓激酶组用博来霉素制备肺纤维化模型,对照组以生理盐水代替博来霉素.制模后第1天起,蚓激酶组每天1次雾化吸入蚓激酶,博来霉素组及对照组吸入等量的生理盐水.第7、14、28天分别处死3组大鼠各8只,行肺组织常规病理及免疫组化检查；测定肺组织匀浆羟脯氨酸含量；测定肺组织匀浆及血浆尿激酶型纤溶酶原激活物(u-PA)、组织型纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制因子1(PAI-1)含量.结果 与博来霉素组相比,蚓激酶组肺泡炎和纤维化程度减轻,肺转化生长因子-β1(TGF-β1)表达减少(P＜0.01).蚓激酶组与博来霉素组相比,第7、14、28天肺组织羟脯氨酸分别为(5.8±2.5)比(9.6±1.3)、(6.7±1.4)比(9.7±1.5)、(7.5±1.2)比(9 7±1.4)mg/L(均P＜0.01)；第7、14天肺组织匀浆u-PA含量分别为(1.04±0.36)比(0.72±0.11)、(0.90±0.09)比(0.75±0.08)μg/L,第14、28天血浆u-PA分别为(0.32±0.04)比(0 25±0.02)、(0.36±0.05)比(0.28±0.04) μg/L(均P＜0.05)；第7、14、28天肺匀浆t-PA分别为(4.70±0.87)比(3.01±0.62)、(5.72±0.37)比(3.00±0.51)、(6.73 ±1.12)比(3.18±0.38)μg/L,血浆t-PA分别为(3.40±0.36)比(1.79±0.38)、(3.17±0.37)比(2.18±0.17)、(3.85±0.56)比(2.80±1.06)μg/L(均P＜0.01)；肺匀浆PAI-1分别为(6.04±0.81)比(8.52±1.01)、(6.78 ±0.81)比(9.81±1.73)、(7.63 +0.99)比(11.44±2.54)μg/L,血浆PAI-1分别为(4.82±0.42)比(6.89±0.84)、(5.73±0.40)比(7.30±1.09)、(5.64±0.87)比(7.98±1.10)μg/L(均P＜0.05).结论 蚓激酶雾化吸入可减轻博来霉素诱发的大鼠肺纤维化,其机制可能是减少了纤溶和抗纤溶的失常.
目的 觀察蚓激酶霧化吸入是否減輕博來黴素誘髮的大鼠肺纖維化及其機製.方法 健康雄性SD大鼠72隻,隨機分為對照組、博來黴素組、蚓激酶組.博來黴素組和蚓激酶組用博來黴素製備肺纖維化模型,對照組以生理鹽水代替博來黴素.製模後第1天起,蚓激酶組每天1次霧化吸入蚓激酶,博來黴素組及對照組吸入等量的生理鹽水.第7、14、28天分彆處死3組大鼠各8隻,行肺組織常規病理及免疫組化檢查；測定肺組織勻漿羥脯氨痠含量；測定肺組織勻漿及血漿尿激酶型纖溶酶原激活物(u-PA)、組織型纖溶酶原激活物(t-PA)、纖溶酶原激活物抑製因子1(PAI-1)含量.結果 與博來黴素組相比,蚓激酶組肺泡炎和纖維化程度減輕,肺轉化生長因子-β1(TGF-β1)錶達減少(P＜0.01).蚓激酶組與博來黴素組相比,第7、14、28天肺組織羥脯氨痠分彆為(5.8±2.5)比(9.6±1.3)、(6.7±1.4)比(9.7±1.5)、(7.5±1.2)比(9 7±1.4)mg/L(均P＜0.01)；第7、14天肺組織勻漿u-PA含量分彆為(1.04±0.36)比(0.72±0.11)、(0.90±0.09)比(0.75±0.08)μg/L,第14、28天血漿u-PA分彆為(0.32±0.04)比(0 25±0.02)、(0.36±0.05)比(0.28±0.04) μg/L(均P＜0.05)；第7、14、28天肺勻漿t-PA分彆為(4.70±0.87)比(3.01±0.62)、(5.72±0.37)比(3.00±0.51)、(6.73 ±1.12)比(3.18±0.38)μg/L,血漿t-PA分彆為(3.40±0.36)比(1.79±0.38)、(3.17±0.37)比(2.18±0.17)、(3.85±0.56)比(2.80±1.06)μg/L(均P＜0.01)；肺勻漿PAI-1分彆為(6.04±0.81)比(8.52±1.01)、(6.78 ±0.81)比(9.81±1.73)、(7.63 +0.99)比(11.44±2.54)μg/L,血漿PAI-1分彆為(4.82±0.42)比(6.89±0.84)、(5.73±0.40)比(7.30±1.09)、(5.64±0.87)比(7.98±1.10)μg/L(均P＜0.05).結論 蚓激酶霧化吸入可減輕博來黴素誘髮的大鼠肺纖維化,其機製可能是減少瞭纖溶和抗纖溶的失常.
목적 관찰인격매무화흡입시부감경박래매소유발적대서폐섬유화급기궤제.방법 건강웅성SD대서72지,수궤분위대조조、박래매소조、인격매조.박래매소조화인격매조용박래매소제비폐섬유화모형,대조조이생리염수대체박래매소.제모후제1천기,인격매조매천1차무화흡입인격매,박래매소조급대조조흡입등량적생리염수.제7、14、28천분별처사3조대서각8지,행폐조직상규병리급면역조화검사；측정폐조직균장간포안산함량；측정폐조직균장급혈장뇨격매형섬용매원격활물(u-PA)、조직형섬용매원격활물(t-PA)、섬용매원격활물억제인자1(PAI-1)함량.결과 여박래매소조상비,인격매조폐포염화섬유화정도감경,폐전화생장인자-β1(TGF-β1)표체감소(P＜0.01).인격매조여박래매소조상비,제7、14、28천폐조직간포안산분별위(5.8±2.5)비(9.6±1.3)、(6.7±1.4)비(9.7±1.5)、(7.5±1.2)비(9 7±1.4)mg/L(균P＜0.01)；제7、14천폐조직균장u-PA함량분별위(1.04±0.36)비(0.72±0.11)、(0.90±0.09)비(0.75±0.08)μg/L,제14、28천혈장u-PA분별위(0.32±0.04)비(0 25±0.02)、(0.36±0.05)비(0.28±0.04) μg/L(균P＜0.05)；제7、14、28천폐균장t-PA분별위(4.70±0.87)비(3.01±0.62)、(5.72±0.37)비(3.00±0.51)、(6.73 ±1.12)비(3.18±0.38)μg/L,혈장t-PA분별위(3.40±0.36)비(1.79±0.38)、(3.17±0.37)비(2.18±0.17)、(3.85±0.56)비(2.80±1.06)μg/L(균P＜0.01)；폐균장PAI-1분별위(6.04±0.81)비(8.52±1.01)、(6.78 ±0.81)비(9.81±1.73)、(7.63 +0.99)비(11.44±2.54)μg/L,혈장PAI-1분별위(4.82±0.42)비(6.89±0.84)、(5.73±0.40)비(7.30±1.09)、(5.64±0.87)비(7.98±1.10)μg/L(균P＜0.05).결론 인격매무화흡입가감경박래매소유발적대서폐섬유화,기궤제가능시감소료섬용화항섬용적실상.
Objective To explore the effects of aerosolized earthworm fibrinolytic enzyme (EFE)on bleomycin-induced pulmonary fibrosis in rats.Methods A total of 72 male SD rats were divided randomly into 3 groups of bleomycin (BLM) group with intratracheal BLM (5 mg/kg),control group with the same dose of normal saline,then after both receiving aerosolization of normal saline once daily instead of EFE,EFE group with EFE (2500 U/kg) by aerosolization once daily after BLM instllation.Lung histopathology,immunohistochemistry for transforming growth factor β1 (TGF-β1),lung hydroxyproline contents,levels of urokinase PA (uPA),tissue plasminogen activator (tPA) and PA inhibitorl (PAI-1) in lung and blood were observed at Days 7,14 and 28 of experiment,respectively.Results Compared with BLM group,pulmonary fibrosis improved and the TGF-β1 expression of lung tissue decreased (P ＜ 0.01).Hydroxyproline content of lung tissue decreased in EFE group compared with BLM group ((5.8 ± 2.5)vs (9.6±1.3),(6.7 ±1.4) vs (9.7 ±1.5),(7.5 ±1.2) vs (9.7± 1.4)mg/L,P＜0.01).Compared with BLM group,the uPA levels of lung were elevated in EFE group at Days 7 and 14 ((1.04 ± 0.36) vs (0.72 ± 0.11),(0.90 ± 0.09) vs (0.75 ± 0.08) μg/L,P ＜ 0.05).Moreover,the plasma levels uPA of increased at Days 14 and 28 ((0.32 ±0.04) vs (0.25 ±0.02),(0.36 ±0.05) vs (0.28 ±0.04) μg/L,P ＜ 0.05).Consistently,conpared with BLM group,the tPA levels of lung increased in EFE group ((4.70±0.87) vs (3.01 ±0.62),(5.72 ±0.37) vs (3.00 ±0.51),(6.73 ± 1.12)vs (3.18 ± 0.38) μg/L,P ＜ 0.01) and the plasma levels of tPA also increased ((3.40 ± 0.36) vs (1.79 ±0.38),(3.17±0.37) vs (2.18±0.17),(3.85±0.56) vs (2.80±1.06) μg/L,P＜0.01).However,compared with BLM group,the PAI-1 levels of lung decreased in EFE group ((6.04 ±0.81) vs (8.52±1.01),(6.78±0.81) vs (9.81 ±1.73),(7.63 +0.99) vs (11.44±2.54),P＜0.05) and the plasma levels of PAI-1 also decreased in EFE group ((4.82 ±0.42) vs (6.89 ±0.84),(5.73 ±0.40) vs (7.30 ±1.09),(5.64±0.87) vs (7.98±1.10) μg/L,P＜0.05).Conclusions Earthworm fibrinolytic enzyme may decrease bleomycin-induced pulmonary fibrosis and TGF-β1 expression while increasing fibrinolytic activation.And fibrinolytic strategies are probably useful for the therapy of fibrotic lung diseases.
