生长激素对血浆蛋白合成代谢的影响

The effects of growth hormone on tumor bearing organism protein anabolism

目的 探讨生长激素（GH）对荷瘤机体血浆蛋白合成代谢的影响及调节的机制.方法 选用30只BALB/c雄性小鼠,接种鼠结肠腺癌细胞株CT26建立小鼠癌症恶病质模型.给予不同时长及剂量的GH注射.测定各组血清总蛋白、白蛋白和血浆白细胞介素（IL）-6浓度;免疫组织化学法测定移植瘤组织增殖细胞核抗原（PCNA）的表达;实时定量聚合酶链反应（Real-time PCR）法测定肝脏组织中细胞因子信号传导抑制蛋白-3（SOCS-3）mRNA的表达.结果 治疗组（C、D、E组）血浆白蛋白浓度明显高于单纯荷瘤组（B组）,且各组的总蛋白、白蛋白差异有统计学意义（P＜0.05）.治疗组小鼠血浆IL-6浓度低于单纯荷瘤组[B组,（310.34±86.06） ng/L],比正常对照组（A组,0 ng/L）高;各组移植瘤中PCNA均有表达,其阳性细胞百分率不同,差异有统计学意义（F=3.14,P ＜0.05）,B组最低[（20.18±3.70）％],E组最高[（29.05±5.01）％];各组肝脏组织中SOCS-3 mRNA相对表达量比较差异有统计学意义（F=7.88,P＜0.01）,E组（0.051 ±0.021）与B组（0.019 ±0.009）比较差异有统计学意义（P＜0.01）.结论 GH可以改善荷瘤机体的营养状况,促进血浆蛋白合成;小剂量、短期应用GH,对改善肿瘤所致低的低蛋白血症是安全、有益的;GH对血浆蛋白代谢影响的机制可能与它上调了肝脏SOCS-3 mRNA的表达和调节IL-6诱导的肝脏急性时相蛋白反应相关.

Objective Through the animal experiment,in order to investigate the effects of growth hormone （GH） plasma protein synthesis metabolism and regulation mechanism.Methods Thirty male BALB/c mice were used to estabilish a mouse model of cancer cachexia which were vaccinated the rat colon adenocarcinoma cell line CT26.These tumor bearing mice were given GH to treatment by different time and dose.Totalprotein,albumin and interleukin （IL）-6 concentrations were determined at the last day of this experiment.And the expression levels of proliferating cell nuclear antigen （PCNA） were determined by immunohistochemical method.And the suppressor of cytokine signaling （SOCS）-3 mRNA expression levels of tumor-bearing mice＇ s live tissue were observed by real-time quantitative polymerase chain reaction （Real-time PCR）.Results Compared with group B,the levels of serum albumin concentration and IL-6 concentration were lower than groups C,D,E.The concentrations of total protein,albumin and IL-6 level showed significant difference between these groups （P ＜ 0.05）.PCNA expression was always positive in each group tumor tissue （F =3.14,P ＜ 0.05）.The percentage of positive cells in each group was different,of which group B （20.18 ±3.70）％ the lowest and group E （29.05 ±5.01）％ the highest.The expression of liver SOCS-3 mRNA also showed significant difference between each group （F =7.88,P ＜ 0.01）,especially group E （0.051 ± 0.02 1） and group B （0.019 ± 0.009,P ＜ 0.01）.Conclusion GH can improve the nutritional status of tumor patients and promote the synthesis of proteins.GH is safe and useful for the cancer-caused hypoalbumineamia by using low dose and short-term.The mechanism of which effect of GH on plasma protein metabolism may be related to the up regulation the expression of liver SOCS-3 mRNA and regulation of IL-6 induced liver acute phase response protein.