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目的观察精氨酸(Arg)对大鼠肝脏分泌胰岛素样生长因子Ⅰ(IGF-Ⅰ)的调控作用,探讨其增强免疫功能的机制。方法Wistar大鼠随机分为正常对照组、创伤对照组及创伤+Arg组,每组8只,后两组大鼠臀部造成软组织创伤。创伤+Arg组伤后给予占饲料总重量5.0%的左旋精氨酸(L-Arg);其余两组大鼠在饲料中添加等重量甘氨酸代替。喂养7d后测定3组大鼠血清中Arg、鸟氨酸(Orn)、生长激素(GH)、一氧化氮(NO)、IGF-Ⅰ水平,并检测其胸腺T淋巴细胞增殖反应能力及肝组织中IGF-ⅠmRNA的表达情况。另用含不同浓度L-Arg的无血清培养基体外培养大鼠原代肝细胞,测定培养上清中IGF-Ⅰ的水平。结果(1)血清Arg、Orn水平:与正常对照组比较,创伤对照组大鼠无明显改变(P>0.05);而创伤+Arg组较其余两组显著升高(P<0.01)。(2)血清GH、NO、IGF-Ⅰ水平:各组大鼠血清GH水平差异无统计学意义(P>0.05)。两组创伤大鼠血清NO水平均低于正常对照组(P<0.01)。创伤对照组血清IGF-Ⅰ水平低于正常对照组(P<0.01),创伤+Arg组较创伤对照组有所升高(P<0.05)。(3)胸腺T淋巴细胞增殖反应能力:创伤对照组显著低于正常对照组(P<0.01),创伤+Arg组较前者明显增强(P<0.01)。(4)肝组织IGF-ⅠmRNA的表达情况:创伤对照组IGF-ⅠmRNA相对丰度为1.08±0.06,低于正常对照组1.19±0.06(P<0.05),创伤+Arg组为1.29±0.06,高于创伤对照组(P<0.01)。(5)肝细胞培养上清中IGF-Ⅰ水平:培养液中L-Arg为0.0750、0.7500、7.5000mmol/L时,IGF-Ⅰ水平较L-Arg为0.0000mmol/L时明显增加(P<0.01);当L-Arg为37.5000mmol/L时,IGF-Ⅰ水平有所下降,但仍高于0.0000mmol/L时(P<0.01)。结论Arg可刺激肝脏IGF-Ⅰ的生成,从而发挥增强机体免疫功能的作用。
Objective To investigate the regulatory effect of arginine (Arg) on the secretion of insulin-like growth factor-Ⅰ (IGF-Ⅰ) in the liver of rats and its mechanism of enhancing immune function. Methods Wistar rats were randomly divided into normal control group, trauma control group and trauma + Arg group, with 8 rats in each group. Soft tissue trauma was caused in buttocks of rats in the latter two groups. The trauma + Arg group was given L-arginine (L-arginine) 5.0% of the total weight of the diet; the other two groups of rats were given the same weight of glycine instead of the feed. Serum Arg, ornithine, growth hormone, nitric oxide and IGF-Ⅰ were measured at 7 days after feeding, and their thymus T lymphocyte proliferative response and liver tissue In the expression of IGF-ⅠmRNA. In addition, rat primary hepatocytes were cultured in vitro with serum-free medium containing different concentrations of L-Arg, and the level of IGF-I in the culture supernatant was measured. Results (1) Serum Arg, Orn levels: Compared with the normal control group, there was no significant change in the trauma control group (P> 0.05); while the traumatic + Arg group was significantly higher than the other two groups (P <0.01). (2) Serum GH, NO, IGF-Ⅰlevels: There was no significant difference in serum GH levels between the two groups (P> 0.05). Serum NO levels in both traumatic rats were lower than those in the normal control group (P <0.01). The level of serum IGF-Ⅰin the trauma control group was lower than that in the normal control group (P <0.01), and the trauma + Arg group was higher than the trauma control group (P <0.05). (3) Proliferative response of thymus T lymphocytes: The wound control group was significantly lower than the normal control group (P <0.01), and the trauma + Arg group was significantly enhanced (P <0.01). (4) The expression of IGF-ⅠmRNA in liver tissue: The relative abundance of IGF-ⅠmRNA in trauma control group was 1.08 ± 0.06, which was lower than 1.19 ± 0.06 (P <0.05) in normal control group and 1.29 ± 0.06 in trauma + Arg group In trauma control group (P <0.01). (5) The level of IGF-Ⅰ in the supernatant of hepatocyte culture: When the concentration of L-Arg in culture medium was 0.0750,0.7500 and 7.5000mmol / L, the level of IGF-Ⅰ was significantly higher than that of L-Arg 0.0000mmol / L (P < 0.01). When L-Arg was 37.5000mmol / L, the level of IGF-Ⅰ decreased but still higher than 0.0000mmol / L (P <0.01). Conclusion Arg can stimulate the production of IGF-Ⅰ in the liver and thus play an important role in enhancing immune function.