切换至 "中华医学电子期刊资源库"
高级检索
中华移植杂志(电子版)

中华移植杂志(电子版) ›› 2021, Vol. 15 ›› Issue (05) : 262 -269. doi: 10.3877/cma.j.issn.1674-3903.2021.05.002

论著

心脏死亡器官捐献大鼠模型肝脏和血清微小核糖核酸表达谱分析
赵纪强1,†(), 赵济全2, 霍枫3, 何朝辉2   
  1. 1. 518033　深圳，中山大学附属第八医院（深圳福田）泌尿外科；510150　广州医科大学附属第三医院器官移植科
    2. 518033　深圳，中山大学附属第八医院（深圳福田）泌尿外科
    3. 510010　广州，中国人民解放军南部战区总医院肝胆外科　肝移植中心
  • 收稿日期:2021-07-12 出版日期:2021-10-25
  • 通信作者: 赵纪强
  • 基金资助:
    深圳市福田区卫生公益性科研项目(FTWS2018077); 广东省器官捐献与移植免疫重点实验室科研项目(2016002)

Expression profiling analysis of microRNA in liver and serum of rat models from donation after cardiac death

Jiqiang Zhao1,†(), Jiquan Zhao2, Feng Huo3, Zhaohui He2   

  1. 1. Department of Urology Surgery, the Eighth Affiliated Hospital of Sun Yat-sen University (Shenzhen Futian) , Shenzhen 518033, China; Department of Organ Transplantation, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China
    2. Department of Urology Surgery, the Eighth Affiliated Hospital of Sun Yat-sen University (Shenzhen Futian) , Shenzhen 518033, China
    3. Department of Hepatobiliary Surgery, Center of Liver Transplantation, General Hospital of the People′s Liberation Army Southern Theater Command, Guangzhou 510010, China
  • Received:2021-07-12 Published:2021-10-25
  • Corresponding author: Jiqiang Zhao
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

赵纪强, 赵济全, 霍枫, 何朝辉. 心脏死亡器官捐献大鼠模型肝脏和血清微小核糖核酸表达谱分析[J]. 中华移植杂志(电子版), 2021, 15(05): 262-269.

Jiqiang Zhao, Jiquan Zhao, Feng Huo, Zhaohui He. Expression profiling analysis of microRNA in liver and serum of rat models from donation after cardiac death[J]. Chinese Journal of Transplantation(Electronic Edition), 2021, 15(05): 262-269.

目的

探究心脏死亡器官捐献(DCD)大鼠模型肝脏和血清微小RNA(miRNA)表达特征。

方法

采用随机数字表法将30只SD大鼠分为DCD组和对照组，每组15只。采用4%水合氯醛腹腔注射进行麻醉后，经腹正中切口剪断膈肌，诱导大鼠低血压和缺氧，进而诱发心脏停跳，构建DCD大鼠模型。对照组未剪断膈肌，麻醉与手术方法同DCD组。模型构建成功后经下腔静脉采血并获取肝脏组织。采用miRNA芯片检测肝脏和血清miRNA表达。采用随机数字表法从DCD组与对照组肝脏差异表达的miRNA中选取部分miRNA，通过实时定量PCR(qRT-PCR)进行验证。选取经qRT-PCR验证的肝脏组织中差异表达的miRNA以及DCD组与对照组肝脏和血清差异表达最显著的部分miRNA，通过miRDB数据库分析预测其靶基因，并进行功能分析。组间正态分布计量资料比较采用成组t检验或单因素方差分析。P<0.05为差异有统计学意义。

结果

DCD组血清ALT、AST和乳酸脱氢酶分别为(76±12)、(286±56)和(2 539±122)U/L，对照组分别为(44±11)、(124±48)和(1 658±126)U/L，差异均有统计学意义(t＝4.622、16.916和16.315，P均<0.05)。DCD组大鼠肝脏组织中38个miRNA表达均高于对照组(Fold Change均>2，P均<0.05)；90个miRNA表达下调(Fold Change均<0.5，P均<0.05)。DCD组大鼠血清10个miRNA表达均高于对照组(Fold Change均>2，P均<0.05)；11个miRNA表达下调(Fold Change均<0.5，P均<0.05)。miR-100-5p、miR-540-3p和miR-10b-5p在肝脏与血清中同步表达上调(Fold Change均>2，P均<0.05)；miR-1843a-5p和miR-342-5p同步表达下调(Fold Change均<0.5，P均<0.05)。qRT-PCR检测结果示：DCD组肝脏组织miR-183-3p、miR-10b-5p、miR-487b-5p、miR-100-5p、miR-503-5p、miR-540-3p和miR-219a-2-3p相对表达均高于对照组，差异均有统计学意义(t＝2.808、6.860、10.106、20.594、3.697、10.433和5.828，P均<0.05)；miR-3559-3p、miR-150-5p、miR-223-3p、miR-340-3p、miR-342-5p、miR-664-2-5p、miR-219b和miR-224-3p相对表达均低于对照组，差异均有统计学意义(t＝-2.726、-3.318、-5.257、-4.845、-4.300、-5.082、-4.546和-3.481，P均<0.05)。miRNA靶基因预测分析显示，上述miRNA的靶基因包含一系列与DCD诱导肝损伤相关的重要生物学过程相关基因。

结论

DCD大鼠肝脏和血清miRNA呈现特异性表达谱，这些失调的miRNA可能成为无创评估DCD供肝损伤的潜在生物标志物。

关键词: 心脏死亡器官捐献, 肝损伤, 微小核糖核酸, 表达谱, 大鼠
Objective

To study the expression characteristics of microRNA (miRNA) in liver and serum of rat models from donation after cardiac death (DCD).

Methods

Thirty SD rats were divided into DCD group and control group with 15 rats in each group by random number table method. After anesthesia by intraperitoneal injection of 4% chloral hydrate, diaphragmatic muscle was cut through abdominal midline incision to induce hypotension and hypoxia in rats, and then cardiac arrest was induced to construct DCD rat model. The anesthesia and operation methods in the control group were the same as those in the DCD group, without cutting the diaphragm. After the model was successfully constructed, blood was collected through inferior vena cava and liver tissue was obtained. miRNA microarray was used to detect the expression of miRNA in liver and serum. Random number table method was used to select some differentially expressed miRNAs in the liver tissue between DCD group and control group, and then were validated by real-time quantitative PCR (qT-PCR). The differentially expressed miRNAs which were verified by qRT-PCR, and some miRNAs with the most significant differentially expressed in liver and serum between the DCD group and the control group were selected, and their potential target genes were predicted and analyzed by miRDB database. Group t test or one-way ANOVA was used for comparison of measurement data of normal distribution between groups. P<0.05 was considered statistically significant.

Results

The serum levels of ALT, AST, lactic dehydrogenase in DCD group were (76±12) U/L, (286±56) U/L, (1 658±126) U/L, all higher than those in control group [(44±11) U/L, (124±48) U/L, (2 539±122) U/L] (t=4.622, 16.916 and 16.315, all P<0.05). The expression of 38 miRNAs in the liver tissues of the DCD group were higher than that of the control group (all Fold Change>2, all P<0.05); 90 miRNAs were significantly down-regulated (all Fold Change <0.5, all P<0.05). The serum levels of 10 miRNAs of the DCD group were higher than that of the control group (all Fold Change>2, all P<0.05); 11 miRNAs were significantly down-regulated (all Fold Change <0.5, all P<0.05). The miR-100-5p, miR-540-3p and miR-10b-5p were up-regulated synchronically in liver and serum (all Fold Change >2, all P<0.05). The simultaneous expression of miR-1843a-5p and miR-342-5p was down-regulated (all Fold Change <0.5, all P<0.05). The results of qRT-PCR showed that the relative expressions of miR-183-3p, miR-10b-5p, miR-487b-5p, miR-100-5p, miR-503-5p, miRr-540-3p and miRr-219a-2-3p in liver tissues in DCD group were all up-regulated and there were statistically significant differences (t=2.808, 6.860, 10.106, 20.594, 3.697, 10.433 and 5.828, all P<0.05). The relative expressions of miR-3559-3p, miR-150-5p, miR-223-3p, miR-340-3p, miR-342-5p, miR-664-2-5, miR-219b and miR-224-3p were all down-regulated and there were statistically significant differences (t=-2.726, -3.318, -5.257, -4.845, -4.300, -5.082, -4.546 and -3.481, all P<0.05). The analysis of predict target genes of miRNAs showed that these miRNAs targeted a series of genes related to important biological processes related to DCD induced liver injury.

Conclusions

Specific expression profiles of miRNAs were found in liver and serum of DCD rats. These disregulated miRNAs could serve as potential non-invasive biomarkers for the assessment of DCD liver injury.

Key words: Donation after cardiac death, Liver injury, MicroRNA, Expression profile, Rat
图1 DCD组和对照组大鼠肝脏组织HE染色结果注：DCD.心脏死亡器官捐献；a~c为对照组，放大倍数分别为×100、×200和×400; d~f为DCD组，放大倍数分别为×100、×200和×400
图2 DCD组和对照组大鼠肝脏miRNA表达聚类分析注：DCD.心脏死亡器官捐献；miRNA.微小核糖核酸；红色示miRNA高表达，绿色示miRNA低表达；rno.大鼠
表1 miRNA靶基因预测及其相关生物学功能及过程
miRNA(靶基因数目) 靶基因(目标分数) 靶基因功能 靶基因生物学过程
miR-369-3p(348) Tle4(100) 激活DNA结合转录因子及RNA聚合酶Ⅱ等 调控DNA转录与RNA聚合酶Ⅱ等
  Ltbp1(99) 结合钙离子和TGF-β等 参与细胞对机械刺激、血小板衍生生长因子刺激的反应等
  Oat(99) 激活N2-乙酰基-L-鸟氨酸：2-酮戊二酸5-氨基转移酶等 参与L-脯氨酸生物合成、精氨酸到谷氨酸的分解代谢等
miR-122-3p(16) Cfap206(95) 编码纤毛和鞭毛相关蛋白等 参与轴丝装配、调节纤毛运动频率等
  Etnk1(88) 激活乙醇胺激酶等 调节磷脂酰乙醇胺合成、蛋白磷酸化等
  Ptbp2(87) 结合信使RNA等 调控小脑发育、RNA剪接负调控等
miR-1b(401) Helz2(99) 激活DNA解旋酶、核受体共激活因子等 参与DNA双链解螺旋及RNA磷酸二酯键水解等
  Mmd(99) 激活蛋白激酶等 正调控神经元分化及调节蛋白激酶活性等
  Slc44a1(98) 激活胆碱跨膜转运蛋白等 参与胆碱转运等
miR-3580-5p(145) Uap1(96) 激活UDP-N-乙酰氨基葡萄糖二磷酸化酶等 参与UDP-N-乙酰氨基葡萄糖合成与代谢等
  Snx2(95) 结合表皮生长因子受体及胰岛素受体等 参与细胞内早期核内体到高尔基体的转运等
  Gabra2(95) 增强γ-氨基丁酸A型受体活性及活化γ-氨基丁酸门控氯离子通道等 调控化学突触信号传递及氨基丁酸信号通路等
miR-100-5p(20) Smarca5(93) 激活ATP水解酶等 调控起始DNA-模板转录及染色质装配等
  Fgfr3(93) 促使ATP、成纤维细胞生长因子结合等 调控细胞外信号调节激酶1/2的级联反应等
  Ap1ar(92) 结合接头蛋白-1复合体、肌动蛋白等 调控细胞内蛋白定位及细胞运动等
miR-503-5p(148) Ccnd1(97) 激活细胞周期蛋白依赖性激酶等 调控细胞周期G1/S期转化、Wnt信号通路等
  Pth(95) 结合甲状旁腺激素受体等 调控蛋白信号转导、激活磷脂酶C等
  Fam122a(95) 抑制蛋白丝氨酸/苏氨酸磷酸酶活性 参与有丝分裂G2/M过渡期检查点调控等
miR-223-3p(237) Gpr155(96) 不明确 参与调控细胞内信号识别和转导等
  Siah1(95) 结合蛋白质羧基末端以调节蛋白质合成等 调控细胞分化和神经元凋亡等
  Alcam(95) 促使同源蛋白质结合 调控适应性免疫反应和轴突延伸等
miR-150-5p(304) Calcr(98) 激活G蛋白偶联受体及淀粉酶受体等 参与G蛋白偶联受体及细胞表面受体相关信号通路等
  Gtpbp3(98) 激活三磷酸鸟苷酶等 参与tRNA甲基化、tRNA对尿苷的修饰等
  Sp1(96) 激活RNA聚合酶Ⅱ等 参与细胞对胰岛素刺激的反应及肝脏发育等
miR-664-2-5p(256) St6galnac6(98) 激活α-N-乙酰半乳糖苷α-2，6-唾液酸转移酶等 参与神经节苷脂生物合成、糖蛋白代谢等
  Rere(97) 促使序列特异性DNA结合等 调控神经分支的形态发育、小脑浦肯野细胞层成熟等
  Arhgap35(96) 结合三磷酸鸟苷酶激活蛋白等 参与轴突导引、轴索束自发性收缩等
miR-3559-3p(125) Grin3a(97) 激活N-甲基-D-天冬氨酸受体及钙离子通道等 参与离子跨膜转运及树突发育等
  Cdc42bpa(95) 促使ATP、同源蛋白质结合等 参与肌动蛋白细胞骨架形成及细胞迁移等
  Tdrd7(94) 促使信使RNA、蛋白氨基端结合等 参与晶状体纤维细胞分化、生殖细胞发育等
miR-540-3p(186) Zbtb4(95) 激活DNA结合转录因子、特异性RNA聚合酶Ⅱ等 调控DNA损伤反应、RNA聚合酶Ⅱ等
  Lipt2(93) 激活脂基(辛酰)转移酶及辛烷酰转移酶等 参与正调控氧代谢过程、蛋白质脂酰化等
  Esf1(93) 促使RNA与蛋白质结合 参与rRNA处理等
miR-10b-5p(115) Adcy7(94) 促进ATP结合、激活腺苷酸环化酶等 调控G蛋白偶联受体信号通路等
  Ipcef1(92) 促使蛋白质结构域特异性结合等 参与细胞质、质膜定位等
  Ddx31(92) 激活RNA解旋酶、RNA结合蛋白等 参与核糖体生物代谢过程等
miR-340-3p(33) Adamts9(93) 增强内肽酶及金属脂肽酶活性等 调控主动脉形态发育、内皮细胞基质黏附等
  Thbd(86) 激活跨膜信号受体、促使钙离子结合等 调控血液凝集等
  Srp54a(77) 激活三磷酸鸟苷酶等 靶向识别膜上颗粒依赖的共翻译蛋白信号等
miR-342-5p(173) Ccar2(95) 促进RNA聚合酶Ⅱ转录起始复合物形成等 参与RNA剪接、线粒体碎片化和细胞凋亡等
  Nav2(95) 激活3′-5′ DNA解螺旋活性等 参与DNA解螺旋、小脑皮层发育等
  Pom121l2(93) 调节核定位序列结合、核孔构成等 调控RNA从细胞核输出、蛋白质进入细胞核等
miR-183-3p(192) Siah1(99) 结合蛋白质羧基末端以调节蛋白质合成等 参与细胞分化、神经元凋亡等。
  Kdm5b(99) 激活氧合酶等 参与细胞对成纤维细胞生长因子刺激的反应等
  Nfyb(96) 激活DNA结合转录刺激因子及特异性RNA聚合酶Ⅱ等 参与RNA聚合酶Ⅱ对转录的正调控等
miR-487b-5p(168) Reep6(97) 无 参与检测视觉感知相关光刺激、调控细胞内转运
  Nell1(96) 激活蛋白激酶C等 调控细胞分化、细胞蛋白质分解代谢等
  Fat4(96) 促使钙离子与膜受体结合等 调控Notch信号通路、细胞黏附等
miR-219a-2-3p(109) Lpar3(95) 激活G蛋白偶联受体等 调控G蛋白偶联受体信号通路等
  Tbk1(94) 促使ATP与酶、蛋白质结合等 调控先天免疫反应等
  Hspa14(94) 激活ATP水解酶等 调控蛋白质折叠及细胞对未折叠蛋白质的反应等
miR-219b(127) Nup205(96) 激活孔蛋白、参与核孔形成等 调控核孔复合体组装等
  Ccdc25(92) 促使DNA与蛋白质结合等 调控细胞运动等
  Mnda(89)) 激活转录共调节因子等 调控B细胞受体信号通路等
miR-224-3p(128) Ppfia2(91) 促使蛋白质与配体结合形成复合体等 调控树突棘发育等
  Prrx1(91) 激活DNA结合转录刺激因子等 参与RNA聚合酶Ⅱ对转录的负调控等
  Exoc2(91) 促使蛋白激酶与蛋白质结合等 调控高尔基体转运等
1
Ortega-deballon I, Homby L, Shemie SD. Protocols for uncontrolled donation after circulatory death: a systematic review of international guidelines practices and transplants outcomes[J]. Crit Care, 2015, 19(1): 268-293.
2
Dubbeld J, Hoekstra H, Farid W, et al. Similar liver transplantation survival with selected cardiac death donors and brain death donors[J]. Br J Surg, 2010, 97(5): 744-753.
3
Zhang L, Zeng L, Gao XP, et al. Transformation of organ donation in China[J]. Transplant Int, 2015, 28(4): 410-415.
4
Nosaka N, Okada A, Tsukahara H. Effects of therapeutic hypothermia for neuroprotection from the viewpoint of redox regulation[J]. Acta Med Okayma, 2017, 71(1): 1-9.
5
中华医学会器官移植学分会. 中国心脏死亡捐献器官评估与应用专家共识[J/CD]. 中华移植杂志：电子版，2014, 8(3): 117-122.
6
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism and function[J]. Cell, 2004, 116(2): 281-297.
7
Lee DD, Croom KP, Shalev JA, et al. Early allograft dysfunction after liver transplantation: an intermediate outcome measure for targeted improvements[J]. Ann Hepatol, 2016, 15(1): 53-60.
8
Shaked A, Chang BL, Bamees MR, et al. An ectopically expressed serum miRNA signature is prognostic, diagnostic, and biologically related to liver allograft rejection[J]. Hepatology, 2017, 65(1): 269-280.
9
Wei L, Gong X, Martinez OM, et al. Differential expression and functions of microRNAs in liver transplantation and potential use as non-invasive biomarkers[J]. Transpl Immunol, 2013, 29(1-4): 123-129.
10
Farid WR, Verhoeven CJ, de Jonge J, et al. The ins and outs of microRNAs as biomarkers in liver disease and transplantation[J]. Transpl Int, 2014, 27(12): 1222-1232.
11
Verhoueven J, Farid WR, De Ruiter PE, et al. MicroRNAs in preservation solution are more predictive of graft quality than their expression in liver tissue[J]. Liver Transplant, 2012, 18(S1): S116.
12
Mas VR, Dumur CI, Scian MJ, et al. MicroRNAs as biomarkers in solid organ transplantation[J]. Am J Transplant, 2013, 13(1): 11-19.
13
Tan L, Jiang W, Lu A, et al. miR-155 aggravates liver ischemia/reperfusion injury by suppressing SOCS1 in mice[J]. Trans Proceed, 2018, 50(10): 3831-3839.
14
Selten JW, Verhoeven CJ, Heedfeld V, et al. The release of microRNA-122 during liver preservation is associated with early allograft dysfunction and graft survival after transplantation[J]. Liver Transplant, 2017, 23(7): 946-956.
15
吕喆，蒋晓刚，廉民学. miR-369-3p对缺氧诱导海马神经元细胞增殖、凋亡的影响及其机制[J]. 海南医学，2020, 31(16): 2041-2047.
16
Sempere LF, Freemantle S, Pitha-Rowe I, et al. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation[J]. Genome Biol, 2004, 5(3): R13.
17
Christodoulou F, Raible F, Tomer R, et al. Ancient animal microRNAs and the evolution of tissue identity[J]. Nature, 2010, 463(7284): 1084-1088.
18
Yan J, Bu XM, Li ZL, et al. Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR-219a-5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1[J]. J Neurochem, 2019, 150(2): 202-217.
19
Wang Y, Zhao J, Zhang C, et al. MiR-219a-2-3p suppresses cell proliferation and promotes apoptosis by targeting MDM2/p53 in pituitary adenomas cells[J]. Biosci Biotechnol Biochem, 2020, 84(5): 911-918.
20
Mitchelson KR, Qin WY. Roles of the canonical myomiRs miR-1, -133 and -206 in cell development and disease[J]. World J Biol Chem, 2015, 6(3): 162-208.
21
Li X, Yuan L, Wang J, et al. MiR-1b up-regulation inhibits rat neuron proliferation and regeneration yet promotes apoptosis via targeting KLF7[J]. Folia Neuropathol, 2021, 59 (1): 67-80.
22
Katano-Toki A, Yoshino S, Nakajima Y, et al. SFPQ associated with a co-activator for PPARγ，HELZ2, regulates key nuclear factors for adipocyte differentiation[J]. Biochem Biophys Res Commun, 2021, 562: 139-145.
23
Wallach T, Wetzel M, Dembny P, et al. Identification of CNS injury-related microRNAs as novel Toll-Like Receptor 7/8 signaling activators by small RNA sequencing[J]. Cells, 2020, 9(1): 186-203.
24
Zhang H, Wang J, Wang Z, et al. Serum miR-100 is a potential biomarker for detection and outcome prediction of glioblastoma patients[J]. Cancer Biomark, 2019, 24(1): 43-49.
25
Azizmohammadi S, Azizmohammadi S, Safari A, et al. The role and expression of miR-100 and miR-203 profile as prognostic markers in epithelial ovarian cancer[J]. Am J Transl Res, 2016, 8(5): 2403-2410.
26
Ge YY, Shi Q, Zheng ZY, et al. MicroRNA-100 promotes the autophagy of hepatocellular carcinoma cells by inhibiting the expression of mTOR and IGF-1R[J]. Oncotarget, 2014, 5(15): 6218-6228.
27
Petrelli A, Perra A, Schernhuber K, et al. Sequential analysis of multistage hepatocarcinogenesis reveals that miR-100 and PLK1 dysregulation is an early event maintained along tumor progression[J]. Oncogene, 2012, 31(42): 4517-4526.
28
Tabet F, Vickers KC, Cuesta Torres LF, et al. HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells[J]. Nat Commun, 2014, 5: 3292.
29
Gimbrone MA Jr, García-Cardeña G. Endothelial cell dysfunction and the pathobiology of atherosclerosis[J]. Circ Res, 2016, 118(4): 620-636.
30
Damani S, Bacconi A, Libiger O, et al. Characterization of circulating endothelial cells in acute myocardial infarction[J]. Sci Transl Med, 2012, 4(126): 126ra33.
31
Singh S, de Ronde MWJ, Kok MGM, et al. MiR-223-3p and miR-122-5p as circulating biomarkers for plaque instability[J]. Open Heart, 2020, 7(1): e001223.
32
Kang H, Tan M, Bishop JA, et al. Whole-exome sequencing of salivary gland mucoepidermoid carcinoma[J]. Clin Cancer res, 2017, 23(1): 283-288.
33
Trifonov S, Houtani T, Shimizu J, et al.GPR155: gene organization, multiple mRNA splice variantsand expression in mouse central nervous system[J]. Biochem Biophys Res Commun, 2010, 398: 19-25.
34
Umeda S, Kanda M, Sugimoto H, et al. Downregulation of GPR155 as a prognostic factor after curative resection of hepatocellular carcinoma[J]. BMC Cancer, 2017, 17(1): 610.
[1] 张巧梅, 孙小平, 李冠胜, 邓扬嘉. 针灸对大鼠呼吸机相关性肺炎中性粒细胞归巢及胞外诱捕网的影响[J]. 中华危重症医学杂志(电子版), 2023, 16(04): 265-271.
[2] 张晓燕, 肖东琼, 高沪, 陈琳, 唐发娟, 李熙鸿. 转录因子12过表达对脓毒症相关性脑病大鼠大脑皮质的保护作用及其机制[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 540-549.
[3] 靳茜雅, 黄晓松, 谭诚, 蒋琴, 侯昉, 李瑶悦, 徐冰, 贾红慧, 刘文英. 产前他克莫司治疗对先天性膈疝大鼠病理模型肺血管重构的影响[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(04): 428-436.
[4] 王迎迎, 谢平. 乙型肝炎病毒感染合并肺结核患者发生肝损伤的危险因素及预测模型构建[J]. 中华实验和临床感染病杂志(电子版), 2023, 17(04): 267-273.
[5] 魏强, 张明祥, 陈强谱, 孙宝房. 增味小承气汤对梗阻性黄疸大鼠胃肠道动力的影响[J]. 中华普通外科学文献(电子版), 2023, 17(04): 267-270.
[6] 吴建永. 单中心2 000例心脏死亡器官捐献肾移植发展与创新[J]. 中华移植杂志(电子版), 2023, 17(04): 0-.
[7] 李义亮, 买买提·依斯热依力, 王永康, 王志, 赛甫丁·艾比布拉, 李赞林, 克力木·阿不都热依木. 聚丙烯和生物补片对腹壁疝大鼠腹横筋膜组织氧化应激、MMPs及TIMPs的影响[J]. 中华疝和腹壁外科杂志(电子版), 2023, 17(02): 125-129.
[8] 杨蕴钊, 周诚, 石美涵, 赵静, 白雪源. 人羊水间充质干细胞对膜性肾病大鼠的治疗作用[J]. 中华肾病研究电子杂志, 2023, 12(04): 181-186.
[9] 付强, 秦丽媛, 李全波. 神经病理性疼痛患者血清miR-15a水平及意义分析[J]. 中华脑科疾病与康复杂志(电子版), 2023, 13(05): 293-298.
[10] 隆昱洲, 柳华, 张云茜, 李兴统, 范云虎, 尚正良, 宋镇妤, 罗丽华. 依达拉奉预适应延长急性缺血性脑卒中溶栓时间窗的研究及ROS/TXNIP/NLRP3通路参与机制的探讨[J]. 中华脑科疾病与康复杂志(电子版), 2023, 13(02): 65-74.
[11] 萨仁高娃, 张英霞, 邓伟, 闫诺, 樊宁. 超声引导下鼠肝消融术后组织病理特征的变化规律及影响[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 394-398.
[12] 王小红, 钱晶, 翁文俊, 周国雄, 朱顺星, 祁小鸣, 刘春, 王萍, 沈伟, 程睿智, 秦璟灏. 巯基丙酮酸硫基转移酶调控核因子κB信号介导自噬对重症急性胰腺炎大鼠的影响及机制[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 422-426.
[13] 马强, 李军, 苟丽娟. 重症急性胰腺炎miR-21-3p、RUNX3表达水平及对病情发展程度的预测[J]. 中华消化病与影像杂志(电子版), 2023, 13(05): 337-341.
[14] 刘艳, 唐神结. 肠道菌群与抗结核药及其所致肝损伤的相关性研究进展[J]. 中华诊断学电子杂志, 2023, 11(02): 82-86.
[15] 戚晓阳, 杨平, 杜忠秋, 邱旭升, 汤黎明, 陈一心. 袖状胃切除术对肥胖合并2型糖尿病大鼠模型骨密度的影响[J]. 中华肥胖与代谢病电子杂志, 2023, 09(02): 102-108.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号