CAJ | 학술논문

目的：探索甘草次酸衍生物 TY501对博莱霉素( BLM)诱导的肺纤维化模型大鼠的抗肺纤维化作用及初步机制。方法将40只大鼠随机分成5组：假手术组、模型组、吡非尼酮组、TY501高剂量组和低剂量组。经气道给予BLM制备大鼠肺纤维化模型，每天灌胃给予受试药。实验结束后，测定肺系数、氧分压( PaO2)，测定 BALF 中 ALB、ALP、LDH以及肺组织中 GSH、HYP含量，测定血清Ⅲ型前胶原( PCⅢ)、Ⅳ型胶原( COL4)含量。结果①肺纤维化早期肺泡炎阶段相关指标：各治疗组与模型组相比，肺系数显著下降( P<0．05)、PaO2明显升高( P<0．05)；与模型组相比，各治疗组大鼠BALF中ALP、ALB以及LDH呈下降趋势(P<0．05)；模型组肺组织匀浆中GSH含量反馈性增高，与假手术组相比存在明显差异(P<0．05)，各治疗组较模型组含量降低(P<0．05)；(2)肺纤维化晚期肺间质纤维化阶段：大鼠肺组织 HYP、血清 PCⅢ( TGF-β通路指标)、血清COL4(MMPs通路指标)含量，各治疗组较模型组呈下降趋势，差异有显著性( P<0．05)。结论 TY501对肺纤维化治疗存在价值，能够减轻 BLM 诱导的肺纤维化程度。 TY501可能通过阻断TGF-β的作用、抑制MMPs等多途径抑制肺纤维化的发生，减轻肺纤维化症状。
목적：탐색감초차산연생물 TY501대박래매소( BLM)유도적폐섬유화모형대서적항폐섬유화작용급초보궤제。방법장40지대서수궤분성5조：가수술조、모형조、필비니동조、TY501고제량조화저제량조。경기도급여BLM제비대서폐섬유화모형，매천관위급여수시약。실험결속후，측정폐계수、양분압( PaO2)，측정 BALF 중 ALB、ALP、LDH이급폐조직중 GSH、HYP함량，측정혈청Ⅲ형전효원( PCⅢ)、Ⅳ형효원( COL4)함량。결과①폐섬유화조기폐포염계단상관지표：각치료조여모형조상비，폐계수현저하강( P<0．05)、PaO2명현승고( P<0．05)；여모형조상비，각치료조대서BALF중ALP、ALB이급LDH정하강추세(P<0．05)；모형조폐조직균장중GSH함량반궤성증고，여가수술조상비존재명현차이(P<0．05)，각치료조교모형조함량강저(P<0．05)；(2)폐섬유화만기폐간질섬유화계단：대서폐조직 HYP、혈청 PCⅢ( TGF-β통로지표)、혈청COL4(MMPs통로지표)함량，각치료조교모형조정하강추세，차이유현저성( P<0．05)。결론 TY501대폐섬유화치료존재개치，능구감경 BLM 유도적폐섬유화정도。 TY501가능통과조단TGF-β적작용、억제MMPs등다도경억제폐섬유화적발생，감경폐섬유화증상。
Aim To investigate TY501′s role in bleo-mycin ( BLM )-induced pulmonary fibrosis in rats. Methods Forty rats were randomly divided into 5 groups, including the sham operation, BLM, PFD, TY501(high and low dose) groups. After administra-tion of BLM intratracheally, PFD and TY501 were giv-en in each group daily, according to the dosage de-signed during 21 days. Lung coefficient, PaO2 were tested before killing the rats. The contents of ALB, ALP, LDH, GSH, HYP were detected by regent kit respectively. PCⅢ and COL4 were determined by ELISA. Results ( 1 ) Some indicators of alveolitis in early stage of IPF: the contents of lung coefficient in three treatment groups were lower and PaO2 was higher than those in BLM group ( P<0. 05 ); compared with BLM group, the contents of ALB, ALP, LDH in the treatment groups reduced on 21 st day ( P<0. 05 );the expression of GSH in BLM group was increased for feedback regulation and higher than the treatment groups and the sham operation group (P<0. 05);(2) some indicators of pulmonary interstitial fibrosis in late stage of IPF:the expressions of HYP, PCⅢand COL4 were reduced after the treatment. There were signifi-cant differences compared with BLM group ( P <0. 05 ) . Conclusions TY501 is valuable for the ther-apy of IPF, the same as the positive drug pirfenidone. TY501 attenuates BLM-induced pulmonary fibrosis, which may be related to the affection of TGF-βpathway and inhibition of MMPs.