吡格列酮对X线照射后成纤维细胞分泌的基质金属蛋白酶-9和基质金属蛋白酶抑制物-1表达的影响

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英文篇名：Influence of Pioglitazone on radiation-induced MMP-9 and TIMP-1 in L929 作者：张一思 ; 刘秀丽 ; 潘洁 ; 刘思涵 ; 王文闻 英文作者：Zhang Yisi;Liu Xiuli;Pan Jie;Liu Sihan;Wang Wenwen;Department of Oncology,the First Affiliated Hospital of Harbin Medical University; 关键词：肺纤维化 ; 成纤维细胞 ; 基质金属蛋白酶9 ; 基质金属蛋白酶抑制剂 ; 吡格列酮 ; 模型 ; 动物 英文关键词：Pulmonary fibrosis;;Fibroblasts;;Matrix metalloproteinase 9;;Matrix metalloproteinase inhibitors;;Pioglitazone;;Models,animal 中文刊名：LZBJ 英文刊名：Chinese Journal of Clinical Healthcare 机构：哈尔滨医科大学附属第一医院肿瘤一科; 出版日期：2019-05-23 15:50 出版单位：中国临床保健杂志 年：2019 期：v.22 基金：黑龙江省卫生计生委科研课题(2016-007) 语种：中文; 页：LZBJ201903024 页数：6 CN：03 ISSN：34-1273/R 分类号：90-95

摘要

目的观察并分析吡格列酮对X射线导致的小鼠肺成纤维细胞(L929细胞)中的基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶抑制物-1(TIMP-1)表达的影响。方法采用RT-PCR法证实L929细胞中具有过氧化物酶体增殖因子活化受体γ(PPAR-γ)表达。采用剂量为10 Gy X射线照射L929细胞,用RT-PCR方法观察照射前与照射后0 h、2 h、7 h、24 h、48 h表达MMP-9和TIMP-1的情况。采用吡格列酮处理上述照射处理过的L929细胞,同上法观察不同时点如上两个指标的表达。结果 RT-PCR检测结果表明L929细胞中存在PPAR-γ的表达。L929细胞经10 Gy照射后其MMP-9表达随照射后时间的延长逐渐增加,在照射后48 h表达最高(F=4. 135,P=0. 022); TIMP-1随照射后时间的延长表达逐渐减少,在照射后48 h表达最低(F=3. 646,P=0. 041)。上述L929细胞经吡格列酮处理后48 h其MMP-9表达降低最明显[0. 76∶0. 52 (F=3. 735,P=0. 024)],其TIMP-1表达升高最明显[0. 17∶0. 27(F=3. 908,P=0. 032)]。结论小鼠L929细胞经X射线照射后出现纤维化相关因子MMP-9表达的升高和TIMP-1表达的降低。吡格列酮可使上述MMP-9高表达降低,使TIMP-1低表达升高。
        Objective To observe and analyze the effect of pioglatazone on the expression of MMP-9,TIMP-1 in mouselungfibroblasts cell( L929 cell) before and after X-ray radiation. Methods RT-PCR method was used to confirm the expression of PPAR-gamma in L929 cells. L929 cells were irradiated with 10 Gy X-ray. The expression of MMP-9 and TIMP-1 in L929 cells was detected by RT-PCR at 0,2,7,24 and 48 hours before and after irradiation. Pioglitazone was used to treat L929 cells irradiated above. The expressions of the above two indices at different time points were tested by the same method. Results The expression of PPAR gamma was detected in L929 cells. After 10 Gy irradiation,the expression of MMP-9 in L929 cells increased gradually with the prolongation of irradiation time,and reached the highest level 48 hours after irradiation( F = 4. 135,P = 0. 022),the expression of TIMP-1 decreased gradually with the prolongation of irradiation time,and the lowest level was found 48 hours after irradiation( F = 3. 646,P = 0. 041). After48 hours of pioglitazone treatment,the MMP-9 level of L929 cells decreased significantly[0. 76∶ 0. 52( F = 3. 735,P =0. 024) ],and the TIMP-1 level increased significantly[0. 17∶0. 27( F = 3. 908,P = 0. 032) ]. Conclusions Pioglitazone can reduce the high expression of MMP-9 and increase the low expression of TIMP-1 in L929 cells after X-ray irradiation.

引文

[1] PARRY T,MOTA R,WILLIS M,et al. The muscle-specific ubiquitin ligase Atrogin-1(MAFbx)inhibits age-associated cardiac fibrosis by enhancing MMP-9 levels in vivo[J]. J Mol Cell Cardi,2017,32(112):166-167.
    [2] GORELOVA I S,SKLYAR L F,MARKELOVA E V,et al. extracellular matrix condition in case of hcvassociated liver fibrosis[J]. Med Immun,2017,19(1):35-44.
    [3] YU S H,LIU L J,LV B,et al. Inhibition of bleomycin-induced pulmonary fibrosis by bone marrow-derived mesenchymal stem cells might be mediated by decreasing MMP9,TIMP-1,INF-γand TGF-β[J]. Cell Biochem Funct,2015,33(6):356-366.
    [4] AVERNA M,BAVESTRELLO M,CRESTA F,et al. Abnormal activation of calpain and protein kinase Cɑpromotes a constitutive release of matrix metalloproteinase 9in peripheral blood mononuclear cells from cystic fibrosis patients[J]. Arch Biochem Biophys,2016,15(604):103-112.
    [5] GUN-ERYILMAZ O,URMAN B,YUKSELTEN Y,et al. A Boza Gene expression levels of MMP-2,MMP-9,TIMP-1and ADAMTS-1 in placentas of IVF/ICSI pregnancies[J/OL]. Fert&Ster,2016,106(3):e350-e350[2018-03-10]. https://www. researchgate. net/publication/307618631_Gene_expression_levels_of_MMP_2_MMP_9_TIMP_1_and_ADAMTS_1_in_placentas_of_IVFICSI_pregnancies. DOI:10. 1016/j. fertnstert. 2016. 07. 993.
    [6] LI J,LIU C,SATO T,et al. Novel antitumor invasive actions of p-Cymene by decreasing MMP-9/TIMP-1 expression ratio in human fibrosarcoma HT-1080 cells[J]. BiolPharm Bull,2016,12(39):1247-1253.
    [7]管春阁,戴岳. PPAR-γ在肺纤维化发生发展中的作用[J].大家健康,2017,11(5):299-302.
    [8] MA Z G,YUAN Y P,ZHANG X,et al. Piperine attenuates pathological cardiac fibrosis via PPAR-γ/AKT pathways[J]. Ebiom,2017,11(18):179-187.
    [9] BAI X,ZHOU Z,LI X,et al. Cdk5 regulates ERK1/2/PPARγ-mediated renal tubulointerstitial fibrosis in diabetic nephropathy[J]. Hong Kong J Nephr,2015,17(2):S11-S12.
    [10] SUN X,LIU Y,LI C,et al. Recent advances of curcumin in the prevention and treatment of renal fibrosis[J/OL].Biomed Res Int,2017[2018-09-10]. https://www. ncbi.nlm. nih. gov/pubmed/28546962. DOI:10. 1155/2017/2418671.
    [11] LIU Q,WANG C Y,LIU Z,et al. Hydroxysafflor yellow A suppresses liver fibrosis induced by carbon tetrachloride with high-fat diet by regulating PPAR-γ/p38 MAPK signaling[J]. Pharm Biology,2014,52(9):1085-1093.
    [12]周瑾,陈香美,刘述文,等. TGF-β1对诱导肾间质成纤维细胞活化并表达MMP-9及TIMP-1的影响[J].解放军医学院学报,2014,35(5):449-453.
    [13]周晓霞,王智彪.曲格列酮上调PPAR-γ抑制宫颈癌He La细胞ICAM-1和MMP-9表达[J].南方医科大学学报,2014,34(11):1693-1696.
    [14]尹鹏,胡君,储著凌,等.替米沙坦通过上调PPAR-γ促进结肠癌SW480细胞TIMP-1表达的实验研究[J].西部医学,2014,26(2):160-162.
    [15]王闯. PPARγ/PTEN/MMP-9信号通路对肝细胞癌侵袭和转移的作用[D].广州:广州医科大学,2014.
    [16]李春陵,朱静雯,王里,等.丹参酮ⅡA磺酸钠对慢性阻塞性肺疾病气道重塑大鼠PPARγ、NF-κB的影响研究[J].贵州医药,2016,40(5):466-468.
    [17] CHUANG C H,YEH C L,YEH S L,et al. Quercetin metabolites inhibit MMP-2 expression in A549 lung cancer cells by PPAR-γassociated mechanisms[J]. J Nutr Bioch,2016,41(33):45-53.
    [18]邹娜,姜丹,刘远远,等. MMP-2、TIMP-2和PPARγ在子痫前期患者胎盘中的表达及意义[J].临床与实验病理学杂志,2016,32(5):488-491.
    [19]熊园园.丹蛭降糖胶囊对2型糖尿病患者血清中TIMP-2、hs-CRP的影响及对糖尿病大鼠肾脏NF-κB的研究[D].合肥:安徽中医药大学,2016.
    [20]刘春丽,商玮,赵凌杰,等.吡格列酮对高脂血症大鼠主动脉组织MMP-2、MMP-9表达的影响[J].河北医药,2014,7(5):659-662.
    [21]徐龙.转化生长因子-β3调控循环纤维细胞在放射性肺纤维化中的作用研究[D].北京:中国人民解放军军事医学科学院,2015.