Zhang Cong, He Jiaqi, Wang Xiaodan, Su Ruiying, Huang Qincheng, Qiao Fang, Qin Chuanjie, Qin Jianguang, Chen Liqiao
Laboratory of Aquaculture Nutrition and Environmental Health, School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, PR China.
Laboratory of Aquaculture Nutrition and Environmental Health, School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, PR China.
Fish Shellfish Immunol. 2022 May;124:480-489. doi: 10.1016/j.fsi.2022.04.028. Epub 2022 Apr 27.
Inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is an immunomodulator to inhibit immune-mediated pro-inflammatory response and has been used to treat various immune-related diseases in mammals. However, the immunoregulatory effect of GABA in crustaceans has not been reported. This study evaluates the regulatory effect of dietary GABA supplementation on the innate immune status and immunoregulatory potential in lipopolysaccharide (LPS)-induced immune response in juvenile Eriocheir sinensis. Juvenile crabs were fed with six diets supplemented with graded GABA levels (0, 40, 80, 160, 320 and 640 mg/kg dry matter) for 8 weeks and then 24 h LPS challenge test was carried out. The results showed that dietary GABA supplementation significantly decreased mortality at 4 and 8 weeks. Moreover, the hemocyanin content, acid phosphatase, and alkaline phosphatase activities significantly increased in the crabs fed GABA supplementation compared with the control. On the contrary, the alanine aminotransferase and alanine aminotransferase activities in serum decreased significantly in the GABA supplementation groups compared with the control. Similarly, superoxide dismutase activity, glutathione content, and the transcriptional expression of the antioxidant-related genes and immune-related genes were significantly higher in the GABA supplementation groups than in the control. In addition, the mRNA expressions of anti-lipopolysaccharide factors (ALF 1, ALF 2, ALF 3) and inflammatory signaling pathways related genes (TLR, Myd88, Relish, LITAF, P38-MAPK, ADAM17) were significantly up-regulated in LPS stimulation groups compared with PBS treatment. Meanwhile, pro-apoptosis-related genes' mRNA expressions were significantly up-regulated, and anti-apoptosis-related genes were significantly down-regulated under LPS stimulation compared with PBS treatment. However, GABA pretreatment effectively alleviated LPS-induced immune overresponse and apoptosis. Therefore, this study demonstrates that dietary GABA supplementation could be used as an immunomodulator to improve the non-specific immunity and antioxidant capacity and alleviate the immune-mediated immune overresponse of juvenile E. sinensis.
抑制性神经递质γ-氨基丁酸（GABA）是一种免疫调节剂，可抑制免疫介导的促炎反应，并已用于治疗哺乳动物的各种免疫相关疾病。然而，GABA在甲壳类动物中的免疫调节作用尚未见报道。本研究评估了日粮中添加GABA对中华绒螯蟹幼蟹先天免疫状态以及脂多糖（LPS）诱导的免疫反应中免疫调节潜力的影响。将幼蟹投喂含不同梯度GABA水平（0、40、80、160、320和640mg/kg干物质）的六种日粮8周，然后进行24小时LPS攻毒试验。结果表明，日粮中添加GABA可显著降低4周和8周时的死亡率。此外，与对照组相比，投喂添加GABA日粮的蟹类血蓝蛋白含量、酸性磷酸酶和碱性磷酸酶活性显著升高。相反，与对照组相比，GABA添加组血清中的谷丙转氨酶和谷草转氨酶活性显著降低。同样，GABA添加组的超氧化物歧化酶活性、谷胱甘肽含量以及抗氧化相关基因和免疫相关基因的转录表达均显著高于对照组。此外，与PBS处理组相比，LPS刺激组中抗脂多糖因子（ALF 1、ALF 2、ALF 3）和炎症信号通路相关基因（TLR、Myd88、Relish、LITAF、P38-MAPK、ADAM17）的mRNA表达显著上调。同时，与PBS处理组相比，LPS刺激下促凋亡相关基因的mRNA表达显著上调，抗凋亡相关基因显著下调。然而，GABA预处理有效减轻了LPS诱导的免疫过度反应和细胞凋亡。因此，本研究表明，日粮中添加GABA可作为一种免疫调节剂，提高中华绒螯蟹幼蟹的非特异性免疫力和抗氧化能力，并减轻免疫介导的免疫过度反应。
