摘要
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(Pa O2),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)、Pa O2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。
Aim To investigate TY501' s role in bleomycin( BLM)-induced pulmonary fibrosis in rats.Methods Forty rats were randomly divided into 5groups,including the sham operation,BLM,PFD,TY501( high and low dose) groups. After administration of BLM intratracheally,PFD and TY501 were given in each group daily,according to the dosage designed during 21 days. Lung coefficient,Pa O2 were tested before killing the rats. The contents of ALB,ALP,LDH,GSH,HYP were detected by regent kit respectively. PC Ⅲ 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 Pa O2 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,PCⅢ and COL4 were reduced after the treatment. There were significant differences compared with BLM group( P <0. 05). Conclusions TY501 is valuable for the therapy of IPF,the same as the positive drug pirfenidone.TY501 attenuates BLM-induced pulmonary fibrosis,which may be related to the affection of TGF-β pathway and inhibition of MMPs.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2015年第2期210-215,共6页
Chinese Pharmacological Bulletin
基金
天津市应用基础与前沿技术研究计划(No 13JCZDJC28500)
天津市应用基础与前沿技术研究计划(No14JCQNJC13000)
