基于蛋白质组学方法探讨四氯化碳诱导的小鼠急性肝损伤的差异蛋白表达

doi:10.13560/j.cnki.biotech.bull.1985.2024-0090

摘要/Abstract

摘要：

目的应用标记定量（TMT）蛋白质组学技术，探究化学诱导剂（carbon tetrachloride，CCl₄）致小鼠急性肝损伤的作用机制。方法 20只SPF级雄性BALB/C小鼠随机分为对照组和诱导组，每组10只，腹腔注射诱导8周（2次/周）。通过测定血液生化水平及肝组织病理切片等指标评价肝损伤的程度。通过串联质谱标记技术（TMT）进行蛋白质组学分析，对发现的差异蛋白进行基因本体论（GO）注释、KEGG通路和蛋白互作网络分析。结果与对照组比较，CCl₄诱导组的血液生化指标谷草转氨酶（aspartate aminotransferase，AST）的值显著升高（P<0.05）；谷丙转氨酶（alanine aminotransferase，ALT）、谷氨酰转肽酶（Y-glutamyl transpeptadase，GGT）、总胆汁酸（total biliary acid，TBA）的值极显著增加（P<0.01），且肝组织病理切片显示CCl₄诱导组小鼠肝损伤明显。利用TMT技术共鉴定了5 955个蛋白，其中440个蛋白强度增加，294个蛋白强度降低，差异蛋白在蛋白表达差异倍数、生物标志物应用和参与经典信号通路（JAK-STAT、PI3K-Akt、Rap1、GnRH、AGE-RAGE）中发挥重要作用。经典信号通路中差异蛋白存在显著富集，且富集程度相对较高。结论 CCl₄作为肝损伤评价的理想化学诱导剂，参与了机体免疫、细胞分裂、凋亡和自噬、炎症和肿瘤形成等多个关键过程，多方向多靶点还原了肝损伤的病理机制，为保肝药物的研发提供了坚实的理论基础和视角。

关键词: 蛋白质组学, 四氯化碳, 肝损伤, 小鼠

Abstract:

Objective Labker quantitative (TMT) proteomics was used to explore the mechanism of chemical inducer (carbon tetrachloride, CCl₄) causing acute liver injury in mice. Method Twenty SPF male BALB/C mice were randomly divided into control and induction groups, with 10 mice in each group, induced by intraperitoneal injection for 8 weeks (2 times/week). The degree of liver injury was evaluated by measuring the blood biochemical level and liver histopathological sections. Proteomic analysis was performed by tandem mass spectrometry labeling technology (TMT), including gene Ontology (GO) annotation, KEGG pathways, and protein interaction network analysis of the found differential proteins. Result Compared with the control group, blood indicator of aspartate aminotransferase (AST) was significantly higher (P<0.05); alanine aminotransferase (ALT), y-glutamyl transpeptadase (GGT), total biliary acid (TBA) (P<0.01). Moreover, liver histopathological sections showed significant liver injury in the CCl₄ induction group. A total of 5 955 proteins were identified using TMT, with 440 increased intensity and 294 decreased, and differential proteins played important roles in protein expression difference, biomarker application and participation in classical signaling pathways (JAK-STAT, PI3K-Akt, Rap 1, GnRH, AGE-RAGE). There was a significant enrichment of differential proteins in classical signaling pathways and a relatively high enrichment. Conclusion CCl₄ as an ideal chemical inducer for liver injury evaluation, it is involved in several key processes such as immunity, cell division, apoptosis and autophagy, inflammation and tumor formation. It reduces the pathological mechanism of liver injury in multiple directions and targets and provides a solid theoretical basis and perspective for the research and development of liver protection drugs.

Key words: proteomics, carbon tetrachloride, liver injury, mice

黎伟华, 吴璟, 金学琴, 雷艳丽. 基于蛋白质组学方法探讨四氯化碳诱导的小鼠急性肝损伤的差异蛋白表达[J]. 生物技术通报, 2025, 41(2): 331-342.

LI Wei-hua, WU Jing, JIN Xue-qin, LEI Yan-li. Exploring the Relative Differential Protein Expression of Carbon Tetrachloride-induced Acute Liver Injury in Mice Based on the Proteomics Method[J]. Biotechnology Bulletin, 2025, 41(2): 331-342.

图/表 7

参考文献 35

1	Lachenmeier DW, Monakhova YB, Rehm J. Influence of unrecorded alcohol consumption on liver cirrhosis mortality [J]. World J Gastroenterol, 2014, 20(23): 7217-7222.
2	Okazaki I, Noro T, Tsutsui N, et al. Fibrogenesis and carcinogenesis in nonalcoholic steatohepatitis (NASH): involvement of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) [J]. Cancers, 2014, 6(3): 1220-1255.
3	Wang S, Lee Y, Kim J, et al. Potential role of Hedgehog pathway in liver response to radiation [J]. PLoS One, 2013, 8(9): e74141.
4	Xie GH, Karaca G, Swiderska-Syn M, et al. Cross-talk between Notch and Hedgehog regulates hepatic stellate cell fate in mice [J]. Hepatology, 2013, 58(5): 1801-1813.
5	Yilmaz Y, Eren F. Serum biomarkers of fibrosis and extracellular matrix remodeling in patients with nonalcoholic fatty liver disease: association with liver histology [J]. Eur J Gastroenterol Hepatol, 2019, 31(1): 43-46.
6	Luckey SW, Petersen DR. Activation of Kupffer cells during the course of carbon tetrachloride-induced liver injury and fibrosis in rats [J]. Exp Mol Pathol, 2001, 71(3): 226-240.
7	Gan DK, Zhang W, Huang CK, et al. Ursolic acid ameliorates CCl₄-induced liver fibrosis through the NOXs/ROS pathway [J]. J Cell Physiol, 2018, 233(10): 6799-6813.
8	Xu GY, Han X, Yuan GX, et al. Screening for the protective effect target of deproteinized extract of calf blood and its mechanisms in mice with CCl₄-induced acute liver injury [J]. PLoS One, 2017, 12(7): e0180899.
9	McCay PB, Lai EK, Poyer JL, et al. Oxygen- and carbon-centered free radical formation during carbon tetrachloride metabolism. Observation of lipid radicals in vivo and in vitro [J]. J Biol Chem, 1984, 259(4): 2135-2143.
10	Saijou E, Enomoto Y, Matsuda M, et al. Neutrophils alleviate fibrosis in the CCl₄-induced mouse chronic liver injury model [J]. Hepatol Commun, 2018, 2(6): 703-717.
11	Li H, Zhang T, Wang K, et al. MFGE8 protects against CCl₄-induced liver injury by reducing apoptosis and promoting proliferation of hepatocytes [J]. J Cell Physiol, 2019, 234(9): 16463-16474.
12	Zhao LD, Jin YH, Donahue K, et al. Tissue repair in the mouse liver following acute carbon tetrachloride depends on injury-induced Wnt/β-catenin signaling [J]. Hepatology, 2019, 69(6): 2623-2635.
13	Liu C, Tao Q, Sun MY, et al. Kupffer cells are associated with apoptosis, inflammation and fibrotic effects in hepatic fibrosis in rats [J]. Lab Invest, 2010, 90(12): 1805-1816.
14	D'Ambrosio R, Aghemo A, Rumi MG, et al. A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis [J]. Hepatology, 2012, 56(2): 532-543.
15	AlSaid M, Mothana R, Raish M, et al. Evaluation of the effectiveness of Piper cubeba extract in the amelioration of CCl₄-induced liver injuries and oxidative damage in the rodent model [J]. Biomed Res Int, 2015, 2015: 359358.
16	Basu S. Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients [J]. Toxicology, 2003, 189(1-2): 113-127.
17	Park CM, Cha YS, Youn HJ, et al. Amelioration of oxidative stress by dandelion extract through CYP2E1 suppression against acute liver injury induced by carbon tetrachloride in Sprague-Dawley rats [J]. Phytother Res, 2010, 24(9): 1347-1353.
18	Son G, Iimuro Y, Seki E, et al. Selective inactivation of NF-kappaB in the liver using NF-kappaB decoy suppresses CCl₄-induced liver injury and fibrosis [J]. Am J Physiol Gastrointest Liver Physiol, 2007, 293(3): G631-G639.
19	Tipoe GL, Leung TM, Liong EC, et al. Epigallocatechin-3-gallate (EGCG) reduces liver inflammation, oxidative stress and fibrosis in carbon tetrachloride (CCl₄)-induced liver injury in mice [J]. Toxicology, 2010, 273(1-3): 45-52.
20	Hsieh CW, Ko WC, Ho WJ, et al. Antioxidant and hepatoprotective effects of Ajuga nipponensis extract by ultrasonic-assisted extraction [J]. Asian Pac J Trop Med, 2016, 9(5): 420-425.
21	Li SQ, Meng HY, Xi SM, et al. The effect of CCl₄-induced acute liver injury on the ADAM8 expression in the mice [C]//2012 International Conference on Biomedical Engineering and Biotechnology. May 28-30, 2012: 589-592.
22	Vladimir-Knežević S, Cvijanović O, Blažeković B, et al. Hepatoprotective effects of Micromeria croatica ethanolic extract against CCl₄-induced liver injury in mice [J]. BMC Complement Altern Med, 2015, 15: 233.
23	Ma JQ, Ding J, Zhang L, et al. Ursolic acid protects mouse liver against CCl₄-induced oxidative stress and inflammation by the MAPK/NF-κB pathway [J]. Environ Toxicol Pharmacol, 2014, 37(3): 975-983.
24	Fu MZ, Yan YC, Su H, et al. Spleen proteome profiling of dairy goats infected with C. pseudotuberculosis by TMT-based quantitative proteomics approach [J]. J Proteomics, 2021, 248: 104352.
25	Klaas M, Kangur T, Viil J, et al. The alterations in the extracellular matrix composition guide the repair of damaged liver tissue [J]. Sci Rep, 2016, 6: 27398.
26	Hao YL, Fang HC, Zhao HL, et al. The role of microRNA-1 targeting of MAPK3 in myocardial ischemia-reperfusion injury in rats undergoing sevoflurane preconditioning via the PI3K/Akt pathway [J]. Am J Physiol Cell Physiol, 2018, 315(3): C380-388.
27	Runge-Morris M, Kocarek TA, Falany CN. Regulation of the cytosolic sulfotransferases by nuclear receptors [J]. Drug Metab Rev, 2013, 45(1): 15-33.
28	Mueller JW, Idkowiak J, Gesteira TF, et al. Human DHEA sulfation requires direct interaction between PAPS synthase 2 and DHEA sulfotransferase SULT2A1 [J]. J Biol Chem, 2018, 293(25): 9724-9735.
29	Bennett BJ, de Aguiar Vallim TQ, Wang ZN, et al. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation [J]. Cell Metab, 2013, 17(1): 49-60.
30	Kovac S, Angelova PR, Holmström KM, et al. Nrf2 regulates ROS production by mitochondria and NADPH oxidase [J]. Biochim Biophys Acta, 2015, 1850(4): 794-801.
31	Xie YL, Chu JG, Jian XM, et al. Curcumin attenuates lipopolysaccharide/d-galactosamine-induced acute liver injury by activating Nrf2 nuclear translocation and inhibiting NF-kB activation [J]. Biomed Pharmacother, 2017, 91: 70-77.
32	Wang QQ, Zhang LL, Yuan XD, et al. The relationship between the bcl-2/bax proteins and the mitochondria-mediated apoptosis pathway in the differentiation of adipose-derived stromal cells into neurons [J]. PLoS One, 2016, 11(10): e0163327.
33	Yang XS, Li Q, Lin X, et al. Mechanism of fibrotic cardiomyopathy in mice expressing truncated Rho-associated coiled-coil protein kinase 1 [J]. FASEB J, 2012, 26(5): 2105-2116.
34	Yang L, Xiong ZY, Zhang LJ, et al. Tumor Necrosis Factor Alpha Down-regulated Human GSTA1 and GSTA4 Expression Through The NF-κB Signaling Pathway in Human Hepatoma HepG2 Cells [J]. Progress in Biochemistry and Biophysics, 2016, 43(8): 801-809.
35	Xie X, Peng J, Chang XT, et al. Activation of RhoA/ROCK regulates NF-κB signaling pathway in experimental diabetic nephropathy [J]. Mol Cell Endocrinol, 2013, 369(1-2): 86-97.

调节（上调/下调） Regulation（Up/Down）	蛋白编号Accession	功能描述 Description	基因符号Gene symbol	分子量Mw/kD	比值（CCl₄/Control） Ratio（CCl₄/Control）	P值 P-value
Up	P50236	Bile salt sulfotransferase 2	Sult2a2	33.3	13.086	1.71E-04
	Q64449	C-type mannose receptor 2	Mrc2	167	5.077	3.11E-04
	P13745	Glutathione S-transferase A1	Gsta1	25.6	4.575	2.36E-03
	Q9R100	Cadherin-17	Cdh17	91.6	3.976	2.38E-04
	P97501	Dimethylaniline monooxygenase ［N-oxide-forming］ 3	Fmo3	60.5	3.438	1.25E-03
	Q6IS41	Solute carrier family 25 member 47	Slc25a47	33.6	3.224	2.49E-02
	Q9CZS1	Aldehyde dehydrogenase X， mitochondrial	Aldh1b1	57.5	3.108	1.66E-05
	Q8BG95	Protein phosphatase 1 regulatory subunit 12B	Ppp1r12b	109	3.007	1.19E-02
Down	Q9QXS8	Probable N-acetyltransferase CML5	Cml5	25.7	0.089	2.98E-03
	Q61694	NADPH-dependent 3-keto-steroid reductase Hsd3b5	Hsd3b5	41.9	0.167	1.24E-03
	Q63836	Selenium-binding protein 2	Selenbp2	52.6	0.156	4.23E-04
	Q60991	Cytochrome P450 7B1	Cyp7b1	58.4	0.169	1.52E-04
	Q9Z0N2	Eukaryotic translation initiation factor 2 subunit 3， Y-linked	Eif2s3y	51.1	0.21	6.87E-05
	O35728	Cytochrome P450 4A14	Cyp4a14	58.7	0.221	1.30E-03
	Q9QXZ6	Solute carrier organic anion transporter family member 1A1	Slco1a1	74.3	0.25	3.72E-04
	Q61646	Haptoglobin	Hp	38.7	0.354	1.78E-02
	P46425	Glutathione S-transferase P 2	Gstp2	23.5	0.393	1.37E-03
	Q3UP75	UDP-glucuronosyltransferase 3A1	Ugt3a1	59.7	0.394	5.09E-04

调节（上调/下调） Regulation（Up/Down）	蛋白编号Accession	功能描述 Description	基因符号Gene symbol	分子量Mw/kD	比值（CCl₄/Control） Ratio（CCl₄/Control）	P值 P-value
Up	P50236	Bile salt sulfotransferase 2	Sult2a2	33.3	13.086	1.71E-04
	Q64449	C-type mannose receptor 2	Mrc2	167	5.077	3.11E-04
	P13745	Glutathione S-transferase A1	Gsta1	25.6	4.575	2.36E-03
	Q9R100	Cadherin-17	Cdh17	91.6	3.976	2.38E-04
	P97501	Dimethylaniline monooxygenase ［N-oxide-forming］ 3	Fmo3	60.5	3.438	1.25E-03
	Q6IS41	Solute carrier family 25 member 47	Slc25a47	33.6	3.224	2.49E-02
	Q9CZS1	Aldehyde dehydrogenase X， mitochondrial	Aldh1b1	57.5	3.108	1.66E-05
	Q8BG95	Protein phosphatase 1 regulatory subunit 12B	Ppp1r12b	109	3.007	1.19E-02
Down	Q9QXS8	Probable N-acetyltransferase CML5	Cml5	25.7	0.089	2.98E-03
	Q61694	NADPH-dependent 3-keto-steroid reductase Hsd3b5	Hsd3b5	41.9	0.167	1.24E-03
	Q63836	Selenium-binding protein 2	Selenbp2	52.6	0.156	4.23E-04
	Q60991	Cytochrome P450 7B1	Cyp7b1	58.4	0.169	1.52E-04
	Q9Z0N2	Eukaryotic translation initiation factor 2 subunit 3， Y-linked	Eif2s3y	51.1	0.21	6.87E-05
	O35728	Cytochrome P450 4A14	Cyp4a14	58.7	0.221	1.30E-03
	Q9QXZ6	Solute carrier organic anion transporter family member 1A1	Slco1a1	74.3	0.25	3.72E-04
	Q61646	Haptoglobin	Hp	38.7	0.354	1.78E-02
	P46425	Glutathione S-transferase P 2	Gstp2	23.5	0.393	1.37E-03
	Q3UP75	UDP-glucuronosyltransferase 3A1	Ugt3a1	59.7	0.394	5.09E-04

疾病 Diseases	相关的蛋白 Related proteins	调节（上调/下调） Regulation（Up/Down）	费希尔精确检验P值Fisher's exact test P value
Proteoglycans in cancer	P05480 Q63844 P51885 P20444 P49710 Q8BG95 P28654 P70336 P49817 P15379 Q01149 Q8BTM8 P70227 P26041 Q9JKF1 P26040 P11276 P11087	Up	7.58E-04
Fluid shear stress and atherosclerosis	Q64337 P05480 P70236 P10648 P16460 Q09014 Q05144 Q64669 P61957 Q5EG47 P49817 Q99L20 P13745 Q60875	Up	1.45E-03
Hypertrophic cardiomyopathy	Q6IRU2 P58771 Q60675 P82347 O54950 Q5EG47 A2ARA8 P31001 P09470	Up	1.53E-03
MicroRNAs in cancer	P20152 P54227 Q63844 P58771 P63280 P20444 D3Z7P3 P21447 Q64261 P15379 P26645 P26040	Up	4.36E-03
Tuberculosis	P05480 Q64449 Q63844 P04441 P19973 Q07813 P51437 O70370 P18242 P11835 O89053 P05555 P08508	Up	6.42E-03
Leishmaniasis	Q63844 P28667 Q09014 P11835 Q61093 P05555 P08508	Up	5.11E-03
Type II diabetes mellitus	Q63844 P52480 Q91W97 O08528 P28867 P17710	Up	2.66E-03
C-type lectin receptor signaling pathway	Q9WVL2 P05480 Q63844 P19973 Q9WTK5 P28867 P70227	Up	3.56E-02
Coronavirus disease-COVID-19	P62918 O09167 P62852 P62849 P62267 P47915 P27659 P61514 P47964 P14115 P62754 P83882 Q9D8E6 P67984 P62830 P62281 Q9CPR4 Q6ZWV7 Q8BP67 P62301 P62751 P41105 P47963 Q9D823 Q9JJI8 P12970 P61255 P61358 Q6ZWV3 P47911 P84099 P62900 Q9D1R9 Q8K182 Q01279 Q8K0E8 Q8VCM7 Q8VCG4 E9PV24 P01029 Q8BH35 P62855	Down	1.72E-20
African trypanosomiasis	Q00623 P02088 P02089 P01942	Down	1.11E-02

疾病 Diseases	相关的蛋白 Related proteins	调节（上调/下调） Regulation（Up/Down）	费希尔精确检验P值Fisher's exact test P value
Proteoglycans in cancer	P05480 Q63844 P51885 P20444 P49710 Q8BG95 P28654 P70336 P49817 P15379 Q01149 Q8BTM8 P70227 P26041 Q9JKF1 P26040 P11276 P11087	Up	7.58E-04
Fluid shear stress and atherosclerosis	Q64337 P05480 P70236 P10648 P16460 Q09014 Q05144 Q64669 P61957 Q5EG47 P49817 Q99L20 P13745 Q60875	Up	1.45E-03
Hypertrophic cardiomyopathy	Q6IRU2 P58771 Q60675 P82347 O54950 Q5EG47 A2ARA8 P31001 P09470	Up	1.53E-03
MicroRNAs in cancer	P20152 P54227 Q63844 P58771 P63280 P20444 D3Z7P3 P21447 Q64261 P15379 P26645 P26040	Up	4.36E-03
Tuberculosis	P05480 Q64449 Q63844 P04441 P19973 Q07813 P51437 O70370 P18242 P11835 O89053 P05555 P08508	Up	6.42E-03
Leishmaniasis	Q63844 P28667 Q09014 P11835 Q61093 P05555 P08508	Up	5.11E-03
Type II diabetes mellitus	Q63844 P52480 Q91W97 O08528 P28867 P17710	Up	2.66E-03
C-type lectin receptor signaling pathway	Q9WVL2 P05480 Q63844 P19973 Q9WTK5 P28867 P70227	Up	3.56E-02
Coronavirus disease-COVID-19	P62918 O09167 P62852 P62849 P62267 P47915 P27659 P61514 P47964 P14115 P62754 P83882 Q9D8E6 P67984 P62830 P62281 Q9CPR4 Q6ZWV7 Q8BP67 P62301 P62751 P41105 P47963 Q9D823 Q9JJI8 P12970 P61255 P61358 Q6ZWV3 P47911 P84099 P62900 Q9D1R9 Q8K182 Q01279 Q8K0E8 Q8VCM7 Q8VCG4 E9PV24 P01029 Q8BH35 P62855	Down	1.72E-20
African trypanosomiasis	Q00623 P02088 P02089 P01942	Down	1.11E-02

[1]	李志强, 王吉英, 袁厅, 王佳, 韦艳娜, 王玉格, 李少丽, 邵国青, 冯志新, 于岩飞. 肺炎支原体感染评价方法的比较研究[J]. 生物技术通报, 2025, 41(1): 110-119.
[2]	陈晓松, 刘超杰, 郑佳, 乔宗伟, 罗惠波, 邹伟. TMT定量蛋白质组学解析Rummeliibacillus suwonensis 3B-1 生长及己酸代谢机制[J]. 生物技术通报, 2024, 40(3): 135-145.
[3]	高登科, 马白荣, 郭怡莹, 刘薇, 刘田, 靳亚平, 江舟, 陈华涛. 利用CRISPR/Cas9技术构建Quaking敲除的小鼠胚胎成纤维细胞株[J]. 生物技术通报, 2024, 40(2): 65-72.
[4]	顾蕾, 张誉露, 唐尚睿, 于浩月, 李辰. 基于质谱的单细胞蛋白质组学技术的发展及应用[J]. 生物技术通报, 2024, 40(11): 125-141.
[5]	许沛冬, 易剑锋, 陈迪, 陈浩, 谢丙炎, 赵文军. 组学技术在生防芽胞杆菌的应用进展[J]. 生物技术通报, 2024, 40(10): 208-220.
[6]	丁亚群, 丁宁, 谢深民, 黄梦娜, 张昱, 张勤, 姜力. Vps28基因敲除小鼠模型的构建及其对泌乳和免疫性状影响的研究[J]. 生物技术通报, 2022, 38(3): 164-172.
[7]	王智博, 王道平, 苗兰, 李瑛, 潘映红, 刘建勋. 血液样本蛋白质组分析方法的比较研究[J]. 生物技术通报, 2021, 37(8): 307-318.
[8]	谢绍怡, 蒋璐蔓, 杨晓峰, 张仙玉, 吴珍芳, 李紫聪. 切割小鼠X染色体的CRISPR/Cas9系统表达载体的构建及验证[J]. 生物技术通报, 2021, 37(5): 67-75.
[9]	张静, 熊燕, 华永琳, 郭玉, 熊显荣, 字向东, 李键. 小鼠骨骼肌纤维类型定量PCR内参基因的筛选[J]. 生物技术通报, 2021, 37(2): 71-79.
[10]	孟丽娜, 彭春莹, 李铁栋, 李博生. 基于蛋白质组学对螺旋藻砷胁迫响应机制的研究[J]. 生物技术通报, 2020, 36(4): 107-116.
[11]	李堃, 刘悦, 黄鹏, 杨智昉, 胡茜, 张颖, 李志宏, 吕叶辉, 梁乐. 小鼠精原细胞分化的蛋白质组学研究[J]. 生物技术通报, 2020, 36(3): 168-176.
[12]	王棋文, 李盼, 潘翠云, 韩芬霞. 乙二醇对体内外源基因表达的作用研究[J]. 生物技术通报, 2019, 35(4): 64-68.
[13]	张良, 陈小青, 宋佳宇, 毛然然, 姜倩雯, 林向民. 巴洛沙星胁迫下大肠杆菌的比较蛋白质组学研究[J]. 生物技术通报, 2019, 35(3): 103-109.
[14]	张达秀, 贺双丽, 王倩, 蒲仕明, 吴琼. 青年和老年小鼠棕色脂肪来源间充质干细胞生物学特性比较[J]. 生物技术通报, 2019, 35(2): 137-142.
[15]	耿慧君, 邹伟, 崔惠敬, 李晓宇, 王丽丽, 徐永平. 基于转录组学的金黄色葡萄球菌噬菌体安全性评估[J]. 生物技术通报, 2019, 35(12): 64-75.