Page 40 - 南京医科大学学报自然科学版

南京医科大学学报（自然科学版） 第44卷第2期
·178 · Journal of Nanjing Medical University（Natural Sciences） 2024年2月

·基础研究·

隐丹参酮通过调节TGF⁃β/Smad通路改善高氧诱导肺损伤的纤

维化过程

马萌萌，包天平，曹林霞，李靖燕，余冰睿，田兆方 *

南京医科大学附属淮安第一医院新生儿科，淮安市小儿呼吸诊疗重点实验室，江苏 淮安 223300

［摘 要］ 目的：探讨隐丹参酮（cryptotanshinone，CTS）对高氧诱导的支气管肺发育不良（bronchopulmonary dysplasia，BPD）大鼠
肺纤维化的影响及作用机制。方法：体内实验：将50只新生雄性SD大鼠随机分为空气组、高氧组、CTS低剂量组（7.5 mg/kg）、CTS
中剂量组（15.0 mg/kg）及CTS高剂量组（30.0 mg/kg）。高氧组及CTS干预组大鼠饲养于氧浓度95％的氧箱中，空气组饲养于空
气中。CTS干预组大鼠生后每日给予CTS腹腔注射，空气组及高氧组每日腹腔注射同等体积DMSO。7 d后安乐死全部大鼠后
取肺组织用于后续实验。应用HE染色观察肺泡病理改变；通过Masson染色观察肺组织纤维化程度；RT⁃qPCR法检测转化生
长因子β1（transforming growth factor⁃β1，TGF⁃β1）及α平滑肌肌动蛋白（α⁃smooth muscle actin，α⁃SMA）的 mRNA 水平；Western
blot 检测细胞信号转导分子（small mother against decapentaplegic，Smad）2/3、p⁃Smad2/3的表达。体外实验：选用人胚肺成纤维
细胞（human fetal lung fibroblast⁃1，HFL⁃1），按照培养条件分为空气组、高氧组及CTS干预组，空气组常规条件下培养，而高氧及
干预组置于95％O2恒温培养箱中培养24 h，干预组加入CTS 10 μmol/L。CCK⁃8实验检测细胞活力；Western blot检测TGF⁃β1、
α⁃SMA、p⁃Smad2/3、Smad2/3蛋白表达变化。结果：与对照组相比，高氧组大鼠肺泡形态紊乱、间隔增宽，RAC值下降，纤维化评
分上升（P<0.05）；TGF⁃β1及α⁃SMA的mRNA水平升高（P<0.05）；p⁃Smad2/3表达升高（P<0.05）；不同剂量的CTS给药后可改善
上述指标（P<0.05）；同时，CTS还可以降低高氧后HFL⁃1细胞的TGF⁃β1、α⁃SMA、p⁃Smad2/3、Smad2/3表达（P<0.05）。结论：CTS
可通过TGF⁃β/Smad通路改善高氧诱导肺损伤的纤维化过程。
［关键词］ 隐丹参酮；高氧；支气管肺发育不良；纤维化
［中图分类号］ R725.6 ［文献标志码］ A ［文章编号］ 1007⁃4368（2024）02⁃178⁃07
doi：10.7655/NYDXBNSN230621

Cryptotanshinone ameliorates the fibrotic process in hyperoxia ⁃ induced lung injury by
modulating the TGF⁃β/Smad pathway
*
MA Mengmeng，BAO Tianping，CAO Linxia，LI Jingyan，YU Bingrui，TIAN Zhaofang
Department of Neonatology，the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University，the
Pediatric Diagnosis and Treatment Respiratory Key Laboratory of Huai’an，Huai’an 223300，China

［Abstract］ Objective：To investigate the effects and underlying mechanism of cryptotanshinone（CTS）on pulmonary fibrosis in rats
with hyperoxia⁃induced bronchopulmonary dysplasia（BPD）. Methods：50 newborn male Sprague⁃Dawley rats were randomly divided
into air group，hyperoxia group，low⁃dose CTS（7.5 mg/kg）group，medium⁃dose CTS（15.0 mg/kg）group and high⁃dose CTS（30 mg/kg）
group. Rats in hyperoxia and three CTS treatment groups were exposed to 95% oxygen（O2 ）for 7 d after birth，and the air group were
exposed to a room environment（21% O2 ）. 7 days later，all rats were euthanized. The alveolar morphology and lung fibrosis were
evaluated using hematoxylin⁃eosin（HE）staining and Masson staining. The mRNA levels of transforming growth factor beta1（TGF⁃β1）
and alpha⁃smooth muscle actin（α⁃SMA）were detected by RT⁃qPCR. The protein expression of cell signaling molecules small mother
against decapentaplegic（Smad）2/3 and p⁃Smad2/3 was detected by Western blot. In vitro experiments：Human fetal lung fibroblasts
（HFL ⁃ 1）cells were selected and divided into air group，hyperoxia group and CTS intervention group according to the culture
conditions. The air group was cultured under conventional conditions，while the hyperoxia and intervention groups were incubated in a

［基金项目］ 江苏省卫生和健康委员会重点项目（ZDB2020005）
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通信作者（Corresponding author），E⁃mail：lyh0729@163.com