Wu Han-Cheng, Hu Qi-Rui, Luo Ting, Wei Wen-Cheng, Wu Hui-Juan, Li Jing, Zheng Liu-Feng, Xu Qun-Ying, Deng Ze-Yuan, Chen Fang
Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, Jiangxi 330006, China.
State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047, China.
Int Immunopharmacol. 2021 Dec;101(Pt B):108316. doi: 10.1016/j.intimp.2021.108316. Epub 2021 Nov 9.
Previously, we reported the octyl ester derivative of ginsenoside Rh2 (Rh2-O) had better antitumor and immunomodulatory effects than Rh2 in H22 tumor-bearing mice. Therefore, this study further explored the effects of Rh2-O on splenic lymphocytes in H22 tumor-bearing mice and the underlying mechanism.
Wild type and Tlr4 mice were selected to establish the H22 tumor-bearing mice model. After the treatment of Rh2-O (10 mg/kg by gavage) for 15 days, the sizes of tumor were measured. Subsequently, the splenic lymphocytes were isolated and the activities (eg. cell proliferation, cytotoxicity and cytokine secretion) were evaluated. Then, the proteins and mRNA expression levels of TRAF6 and NF-ĸB p65 in splenic lymphocytes were examined.
The results showed that Rh2-O administration enhanced the proliferative capacity and cytotoxicity of splenic lymphocytes, and the effects were Tlr4-associated. Compared to WT mice, the up-regulation of cytokines secretion (eg. IFN-γ, IL-2 and IL-4) in isolated splenic lymphocytes after Rh2-O administration was lower in Tlr4 mice. Moreover, the results showed Rh2-O increased the expression of TRAF6 and the level of endonuclear NF-ĸB p65, which was inhibited in Tlr4 mice (P < 0.05).
Rh2-O could exert immunomodulatory effects on splenic lymphocytes with the partial participation of TLR4 in H22 tumor-bearing mice.
此前，我们报道了人参皂苷Rh2的辛酯衍生物（Rh2-O）在荷H22肿瘤小鼠中比Rh2具有更好的抗肿瘤和免疫调节作用。因此，本研究进一步探讨了Rh2-O对荷H22肿瘤小鼠脾淋巴细胞的影响及其潜在机制。
选用野生型和Tlr4基因敲除小鼠建立荷H22肿瘤小鼠模型。经Rh2-O（10mg/kg灌胃）处理15天后，测量肿瘤大小。随后，分离脾淋巴细胞并评估其活性（如细胞增殖、细胞毒性和细胞因子分泌）。然后，检测脾淋巴细胞中TRAF6和NF-κB p65的蛋白和mRNA表达水平。
结果显示，给予Rh2-O可增强脾淋巴细胞的增殖能力和细胞毒性，且这些作用与Tlr4相关。与野生型小鼠相比，给予Rh2-O后，Tlr4基因敲除小鼠分离的脾淋巴细胞中细胞因子分泌（如IFN-γ、IL-2和IL-4）的上调程度较低。此外，结果显示Rh2-O增加了TRAF6的表达和细胞核内NF-κB p65的水平，而在Tlr4基因敲除小鼠中这种增加受到抑制（P<0.05）。
在荷H22肿瘤小鼠中，Rh2-O可在TLR4部分参与下对脾淋巴细胞发挥免疫调节作用。
