大黄牡丹汤对胰腺癌大鼠的治疗作用和肝肾保护作用

doi:10.13481/j.1671-587x.20170601

摘要/Abstract

摘要： 目的：通过二甲基苯蒽（DMBA）胰腺包埋法制备大鼠胰腺癌模型，探讨大黄牡丹汤对模型大鼠胰腺癌的治疗作用及对胰腺癌大鼠肝肾功能的保护作用，并阐明其作用机制。方法：65只SD雄性大鼠分为空白组（10只）和造模组（55只）。造模组大鼠胰腺被膜下包埋DMBA，建立胰腺癌大鼠模型。3个月后，选取造模成功的50只大鼠随机分为模型组、氟尿嘧啶组（静脉注射给药，12 mg·kg^-1）和低、中、高剂量大黄牡丹汤组（灌胃给药，20、40、80 mg·kg^-1）。给药10周后，检测大鼠血清中丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、尿素氮（BUN）、肌酐（Cr）及总胆红素（TBiL）水平；称胰腺肿瘤质量计算肿瘤抑制率；TUNEL法检测胰腺肿瘤组织中细胞凋亡率；Q-PCR法检测胰腺肿瘤组织中SST2R、Bax及Bcl-2基因的表达水平。结果：与模型组比较，给药10周后，低、中和高剂量大黄牡丹汤组大鼠血清中ALT、AST、BUN、Cr及TBiL水平明显降低（P<0.05或P<0.01）；中和高剂量大黄牡丹汤组大鼠肿瘤质量明显降低（P<0.05或P<0.01）；低、中和高剂量大黄牡丹汤组大鼠胰腺肿瘤组织中细胞凋亡率明显升高（P<0.05或P<0.01）；低、中和高剂量大黄牡丹汤组大鼠胰腺肿瘤组织中SST2R基因表达水平明显升高（P<0.05或P<0.01）；中和高剂量大黄牡丹汤组大鼠胰腺肿瘤组织中Bax基因表达水平明显升高（P<0.05或P<0.01），Bcl-2基因表达水平明显降低（P<0.05）。结论：大黄牡丹汤具有治疗大鼠胰腺癌的作用，可以促进肿瘤细胞凋亡，同时能够保护胰腺癌大鼠的肝肾功能。

关键词: 大黄牡丹汤, 二甲基苯蒽, 胰腺肿瘤, 细胞凋亡

Abstract: Objective:To establish the pancreatic carcinoma models of rats with dimethybenzanthracene(DMBA) embedding method, to discuss the treatment effect of Da Huang Mu Dan Tang (DHMDT) in the rats with pancreatic carcinoma and the protective effects on the liver and kidney function, and to clarify the mechanisms. Methods:Sixty-five SD male rats were divided into blank control (n=10) and modeling group (n=55). DMBA was embedded in the capsule of pancreas to establish the pancreatic carcinoma models of rats. After 3 months, 50 successfully modeling rats were randomly divided into model, 5-FU (intravennous injection, 12 mg·kg^-1), low, middle and high doses of DHMDT (intragastric administration, 20,40 and 80 mg·kg^-1) groups. After 10 weeks of administration, the levels of alanine aminotransferase(ALT), aspartate transaminase(AST), urea nitrogen(BUN), creatinine(Cr) and total bilirubin(TBiL) in serum of the rats in various groups were measured; the weights and the inhibitory rates of the pancreatic tumor were detected; TUNEL method was used to analyze the apoptotic rates of tumor tissue; the expression levels of SST2R, Bax and Bcl-2 genes in pancreatic tumor tissue of the rats were detected by Q-PCR method. Results:Compared with model group, after treated for 10 weeks, the levels of ALT, AST, BUN, Cr and TBiL in serum of the rats in low, middle and high doses of DHMDT groups were significantly decreased (P<0.05 or P<0.01); the weights of tumor of the rats in middle and high doses of DHMDT groups were decreased (P<0.05 or P<0.01); the apoptotic rates of the cells in pancreatic tumor tissue of the rats in low, middle and high doses of DHMDT groups were increased (P<0.05 or P<0.01); the expression levels of SST2R gene in pancreatic tumor tissue of the rats in low, middle and high doses of DHMDT groups were significantly increased (P<0.05 or P<0.01); the expression levels of Bax gene in pancreatic tumor tissue of the rats in middle and high doses of DHMDT groups were significantly increased(P<0.05 or P<0.01), while the expression levels of Bcl-2 in pancreatic tumor tissue of the rats were significantly decreased (P<0.05). Conclusion:DHMDT has the treatment effect in the rats with pancreatic carcinoma and can promote the apoptosis of tumor cells;DHMDT can protect the liver and kidney function of the rats with pancreatic carcinoma.

Key words: Da Huang Mu Dan Tang, dimethybenzanthracene, apoptosis, pancreas neoplasms

中图分类号:

R735.9

王云检, 张珉, 蒙博, 尤国华. 大黄牡丹汤对胰腺癌大鼠的治疗作用和肝肾保护作用[J]. 吉林大学学报(医学版), 2017, 43(06): 1069-1073.

WANG Yunjian, ZHANG Min, MENG Bo, YOU Guohua. Treatment effect of Da Huang Mu Dan Tang in rats with pancreatic carcinoma and protective effects on liver and kindey function[J]. Journal of Jilin University Medicine Edition, 2017, 43(06): 1069-1073.

参考文献

[1] 李慧超, 王宁, 郑荣寿, 等. 中国2010年胰腺癌发病和死亡分析[J]. 中国肿瘤, 2015,24(3):163-169.
[2] 刘海林, 王磊. 胰腺癌早期诊断与治疗的研究进展[J]. 世界华人消化杂志, 2009,17(34):3475-3479.
[3] 金莉. 胰腺癌中医治疗进展[J]. 浙江中医杂志, 2012,47(11):855-857.
[4] 胡英兴, 胡望景, 吴斌斌. 大黄牡丹汤不同给药途径治疗阑尾脓肿的临床疗效观察[J]. 中国中医药科技, 2016,23(1):62-63.
[5] 张艳霞, 张延英, 舒畅, 等. 大黄牡丹汤组方对急性胰腺炎大鼠的保护作用[J]. 中医研究, 2015,28(2):55-58.
[6] 刘丽, 尹运涵, 吴健, 等. HPLC法同时测定大黄牡丹汤中大黄酸、丹皮酚和芍药苷的含量[J]. 中国药物警戒, 2010,7(3):139-141.
[7] Satake K, Yoshimoto T, Mukai R, et al. Estrogen receptors in 7,12-dimethylbenz (a) anthracene (DMBA) induced pancreatic carcinoma in rats and in human pancreatic carcinoma[J]. Clin Oncol, 1982,8(1):49-54.
[8] 敖澜. 高强度聚焦超声消融胰腺原位癌后大鼠胰岛结构和内分泌功能的转归[D]. 重庆:西南大学, 2016.
[9] 李清龙. SD大鼠胰腺癌模型及其DNA损伤修复蛋白和癌干细胞标记蛋白在诱癌中的作用[D]. 长沙:中南大学, 2009.
[10] Yamada R, Tanaka K, Naota H, et al. A long surviving case with undifferentiated pancreatic carcinoma[J]. Intern Med, 2016,55(22):3403-3404.
[11] Danoy M, Shinohara M, Rizki-Safitri A, et al. Alteration of pancreatic carcinoma and promyeloblastic cell adhesion in liver microvasculature by co-culture of hepatocytes, hepatic stellate cells and endothelial cells in a physiologically-relevant model[J]. Integr Biol (Camb), 2017,9(4):350-361.
[12] Wang L, Liu H L, Li Y, et al. Proteomic analysis of pancreatic intraepithelial neoplasia and pancreatic carcinoma in rat models[J]. World J Gastroenterol, 2011,17(11):1434-1441.
[13] Li F, El-Dika S, Modi R M, et al. Poorly differentiated pancreatic carcinoma with sarcomatoid differentiation:confocal endomicroscopy of an uncommon pancreatic cystic lesion[J]. Endoscopy, 2016,48(S01):E363-E364.
[14] Xi H, Fan X, Zhang Z, et al. Bax and Bcl-2 are involved in the apoptosis induced by local testicular heating in the boar testis[J]. Reprod Domest Anim, 2017,52(3):359-365.
[15] Qin RY, Fang RL, Gupta MK, et al. Alteration of somatostatin receptor subtype 2 gene expression in pancreatic tumor angiogenesis[J]. World J Gastroenterol, 2004,10(1):132-135.
[16] 秦仁义, 裘法祖. 奥曲肽对胰腺癌组织SST2R和SST2R mRNA表达的影响[J]. 胰腺病学, 2002(1):41-44.