Zhuang Cuicui, Liu Dawei, Yang Xu, Wang Haoran, Han Lulu, Li Yanfei
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Heilongjiang Province Hospital, Harbin 150036, China; School Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
Chemosphere. 2016 Apr;149:34-40. doi: 10.1016/j.chemosphere.2016.01.084. Epub 2016 Feb 2.
The previous research found that norepinephrine (NE) enhanced the immunotoxicity of aluminum trichloride (AlCl3) on rat peritoneal macrophages in vitro through activating the β2-adrenoceptors (β2-AR)/cAMP pathway. On that basis, the experiment in vivo was conducted in this experiment. Eighty Wistar rats were orally exposed to 0 (control group); 0.4 mg/mL (low-dose group); 0.8 mg/mL (mid-dose group) and 1.6 mg/mL (high-dose group) AlCl3 for 120 days, respectively. Aluminum (Al), NE, macrophage migration inhibitory factor (MIF) and tumor necrosis factor-α (TNF-α) contents in serum, cAMP content, β2-AR density, mRNA expressions of TNF-α, MIF and β2-AR in rat peritoneal macrophages were examined. These results showed that AlCl3 increased serum Al and NE contents, peritoneal macrophages cAMP content, the density and mRNA expression of the β2-AR, and decreased serum MIF and TNF-α contents, peritoneal macrophages mRNA expressions of MIF and TNF-α. Serum NE content was negatively correlated with serum TNF-α and MIF contents and peritoneal macrophages mRNA expressions of TNF-α and MIF, but positively correlated with cAMP content, density of β2-AR and mRNA expression of β2-AR of peritoneal macrophages. It indicated that AlCl3 suppresses peritoneal macrophages function of rats through β2-AR/cAMP pathway acted by NE.
先前的研究发现，去甲肾上腺素（NE）通过激活β2-肾上腺素能受体（β2-AR）/环磷酸腺苷（cAMP）途径增强了三氯化铝（AlCl3）对大鼠腹腔巨噬细胞的体外免疫毒性。在此基础上，本实验进行了体内实验。80只Wistar大鼠分别口服0（对照组）；0.4mg/mL（低剂量组）；0.8mg/mL（中剂量组）和1.6mg/mL（高剂量组）的AlCl3，持续120天。检测血清中铝（Al）、NE、巨噬细胞移动抑制因子（MIF）和肿瘤坏死因子-α（TNF-α）的含量，cAMP含量，β2-AR密度，以及大鼠腹腔巨噬细胞中TNF-α、MIF和β2-AR的mRNA表达。这些结果表明，AlCl3增加了血清Al和NE含量、腹腔巨噬细胞cAMP含量、β2-AR的密度和mRNA表达，并降低了血清MIF和TNF-α含量、腹腔巨噬细胞MIF和TNF-α的mRNA表达。血清NE含量与血清TNF-α和MIF含量以及腹腔巨噬细胞TNF-α和MIF的mRNA表达呈负相关，但与cAMP含量、β2-AR密度和腹腔巨噬细胞β2-AR的mRNA表达呈正相关。这表明AlCl3通过NE作用的β2-AR/cAMP途径抑制大鼠腹腔巨噬细胞的功能。
