L-精氨酸在人肝癌裸鼠肝脏移植瘤生长中的作用

目的 探讨L-精氨酸(L-arg)在人肝癌裸鼠肝脏移植瘤生长中的作用.方法 建立人肝癌裸鼠肝脏移植瘤模型,使用L-arg进行干预治疗,采用免疫组化方法 和图像分析技术检测增殖细胞核抗原(PCNA)的表达,原位末端标记(TUNEL)法检测肿瘤细胞的凋亡情况.结果 (1)小剂量L-arg(0.5 g·kg~(-1)·d~(-1))组、大剂量L-arg(1g·kg~(-1)·d~(-1))组和对照组移植瘤重量分别为(985±76)mg、(328±35)mg、(586±56)mg;大剂量L-arg组移植瘤重量较对照组显著减少(P＜0.05);小剂量L-arg组移植瘤重量较对照组显著增加(P＜0.05).(2)大剂量L-arg组移植瘤PCNA的表达较对照组显著下调(P＜0.05),小剂量L-arg组和对照组比较无明显差异(P＞0.05).(3)大剂量L-arg组NO水平较对照组和小剂量组显著升高(P＜0.05),小剂量L-arg较对照组显著升高(P＜0.05).(4)大剂量L-arg组移植瘤凋亡指数(AI)明显高于对照组(P＜0.05);小剂量L-arg对移植瘤AI无明显影响(P＞0.05).结论 L-精氨酸对肝癌具有双重作用.小剂量L-精氨酸可促进肝癌生长;大剂量L-精氨酸抑制肝癌的生长.

Effects of L-arginine on tumor growth of human hepatocellular carcinoma in nude mice

Objective To study the effects of L-arginine(L-arg)on tumor growth of human hepatocellular carcinoma(HCC)in nude mice.Methods Tumor tissues of HCC were implanted into the liver of nude mice.Then,nude mice were treated with L-arginine.Immunohistochemical staining and image analysis were used to detect the protein expression of proliferating cell nuclear antigen(PCNA).Tumor apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling(TUNEL)assay.Results(1)The tumor weight was(985±76)mg,(328±35)mg and(586±56)mg in L-arg(0.5 g·kg~(-1)·d~(-1)),L-arg~(-1) g·kg~(-1)·d~(-1))and control group respectively.The tumor weight was significantly decreased in L-arg(1 g·kg~(-1)·d~(-1) group and significantly increased in L-arg(0.5 g·kg~(-1)·d~(-1))group as compared with the control group(P＜0.05).(2)The protein expression of PCNA was remarkably down-regulated in L-arg(1 g·kg~(-1)·d~(-1))group than in the control group(P＜0.05)and were not remarkably different between L-arg(0.5 g·kg~(-1)·d~(-1))group and the control(P＞0.05).(3)Serum nitric oxide(NO)concentration was significantly increased in L-arg(1 g·kg~(-1)·d~(-1))group as compared with L-arg(0.5 g·kg~(-1)·d~(-1))group(P＜0.05),significantly in-creased in L-arg(0.5 g·kg~(-1)·d~(-1))group as compared with control group(P＜0.05).(4)Comparing with the control,the apoptosis index of tumor cell was significantly higher in L-arg(1g·kg~(-1)·d~(-1))group (P＜0.05),and there was no difference in L-arg(0.5 g·kg~(-1)·d~(-1))group(P＞0.05).Conclusion L-arginine may have a dual pro-and anti-tumor action on HCC.When it is at high concentrations,L-arginine has antitumor activity.It may promote the growth of HCC at a low concentration.