CAJ | 학술논문

背景与目的肺纤维化是肺癌放化疗后的常见病理改变，是阻碍药物转运到肺部的关键因素之一，肽转运载体已经成为合理设计肽和肽类药物的靶标，本研究旨在探讨肽转运载体2（peptide transporter 2, PEPT2） mRNA在肺纤维化大鼠肺组织中的表达。方法健康SD大鼠50只，随机分为5组。博莱霉素（bleomycin, BLM）7 d、14 d、28 d组：气管内一次性滴入博莱霉素溶液复制肺纤维化大鼠模型，分别于给药后7 d、14 d和28 d放血处死；生理盐水组滴入等量生理盐水，于14 d放血处死；正常组不做任何处理。各组取肺组织，光镜观察组织病理变化；检测样本羟脯氨酸含量；半定量RT-PCR检测肺组织PEPT2 mRNA表达。结果 BLM 7 d组大鼠肺组织呈急性炎症性改变，无纤维增生；BLM 14 d组和28 d组大鼠肺组织均有纤维化改变，以28 d组最为明显。BLM 7 d组肺组织羟脯氨酸含量与正常对照组和生理盐水组相比无统计学差异（P>0.05）；14 d组和28 d组大鼠肺组织羟脯氨酸含量均高于正常对照组和生理盐水组（P<0.05）。各组肺组织PEPT2 mRNA的相对表达量无统计学差异（P>0.05）。结论 PEPT2 mRNA在博莱霉素致肺纤维化大鼠肺组织表达水平无明显变化，PEPT2可能是设计肺纤维化的新型肽类药物靶标之一。
배경여목적폐섬유화시폐암방화료후적상견병리개변，시조애약물전운도폐부적관건인소지일，태전운재체이경성위합리설계태화태류약물적파표，본연구지재탐토태전운재체2（peptide transporter 2, PEPT2） mRNA재폐섬유화대서폐조직중적표체。방법건강SD대서50지，수궤분위5조。박래매소（bleomycin, BLM）7 d、14 d、28 d조：기관내일차성적입박래매소용액복제폐섬유화대서모형，분별우급약후7 d、14 d화28 d방혈처사；생리염수조적입등량생리염수，우14 d방혈처사；정상조불주임하처리。각조취폐조직，광경관찰조직병리변화；검측양본간포안산함량；반정량RT-PCR검측폐조직PEPT2 mRNA표체。결과 BLM 7 d조대서폐조직정급성염증성개변，무섬유증생；BLM 14 d조화28 d조대서폐조직균유섬유화개변，이28 d조최위명현。BLM 7 d조폐조직간포안산함량여정상대조조화생리염수조상비무통계학차이（P>0.05）；14 d조화28 d조대서폐조직간포안산함량균고우정상대조조화생리염수조（P<0.05）。각조폐조직PEPT2 mRNA적상대표체량무통계학차이（P>0.05）。결론 PEPT2 mRNA재박래매소치폐섬유화대서폐조직표체수평무명현변화，PEPT2가능시설계폐섬유화적신형태류약물파표지일。
Background and objective Pulmonary ifbrosis is a common pathological phenomenon in lung cancer patients atfer chemotherapy or radiotherapy. It is also a key hindrance to the transport of drugs to lung tissue. Peptide trans-porters have become a target of the rational design of peptides and peptide drugs. hTe aim of this study is to investigates the expression of peptide transporter 2 (PEPT2) mRNA in the lungs of rats with bleomycin (BLM)-induced pulmonary ifbrosis. Methods Fitfy healthy adult Sprague-Dawley rats were randomly divided into ifve groups. One group was untreated (control), the second group was injected with normal saline solution (NS), and the three remaining groups were treated with a single dose of bleomycin to induce pulmonary ifbrosis (BLM). Rats from the NS group were killed by exsanguination on day 14. Rats from the BLM group were killed by exsanguination on days 7, 14, and 28. hTe lung samples were observed under light microscopy and the hydroxyproline concentration was determined. hTe expression levels of PEPT2 mRNA were measured by RT-PCR. Results hTe morphological study showed that collagenous ifber proliferated in the lungs of rats injected with BLM, indicating pulmonary ifbrosis. hTis proliferation was apparent at 14 d post-injection and especially at 28 d post-injection. Hydroxyproline levels increased seven days post-injection compared with the control group and NS group, but there was no signiifcant statisti-cal difference (P>0.05). Hydroxyproline levels signiifcantly increased (P<0.05) 14 d and 28 d post-infection. hTe change in the lung tissue pathology coincided with the change in hydroxyproline levels. hTere were no signiifcant changes of pulmonary PEPT2 mRNA expression levels among the different groups (P>0.05). Conclusion PEPT2 is a potential peptide drug target in the treatment of pulmonary ifbrosis, although there were no signiifcant changes of PEPT2 mRNA expression in the lungs of rats with bleomycin-induced pulmonary ifbrosis.