Interventional Effect And Mechanism Of Melatonin On Inhibition Of Immune Function In Spleen Of Rats Exposed To Aluminum

Aluminum is an immunotoxin,and long-term exposure or excessive intake can accumulate in immune tissues,which can lead to immunosuppression.Oxidative stress and apoptosis are important pathological mechanisms of aluminum-induced immunosuppression.The spleen is one of the main target organs of aluminum accumulation.Melatonin?MT?,an endogenous methoxysteroid hormone,can improve immunity,resist oxidative stress and impede abnormal apoptosis.In addition,MT can reduce the accumulation of aluminum in the body and resist aluminum-induced multi-organ toxicity,but whether MT can alleviate aluminum-induced spleen immunosuppression has not been reported.In this study,MT alleviating aluminum-induced immunosuppression was used as a theoretical hypothesis.Wistar rats were randomly divided into control group?CG?,aluminum treated group?AG?,MT intervention group?AMG?and MT control group?MG?.The spleen structure and function,oxidative stress status,apoptosis level and expression of Nrf2 signaling pathway were measured to evaluate the effect and mechanism of MT on splenic immunosuppression in rats exposed to aluminum.The results showed that:?1?Compared with CG,the body weight,spleen weight and spleen coefficient in AG were significantly decreased?p<0.01?.Compared with AG,the above results were significantly increased in AMG?p< 0.01?,indicating that MT can alleviate the growth retardation induced by aluminum in rats.The boundaries between white,red and marginal region in CG rats were clear,the structure was complete,and the arrangement was neat.The boundary between red and white pulp in AG was vague,the cells were arranged disorderly,the marginal region was missing,and the central artery was swollen.The boundary between red and white pulp in AMG was clear,only the marginal region was slightly missing.MG was similar to structure of CG,indicating that MT attenuated aluminum-induced inhibition of spleen growth and development.?2?Compared with CG,the CD³⁺ and CD⁴⁺,CD⁴⁺/CD⁸⁺ and IL-2,IL-4,IL-6,IL-10,TNF-? and IFN-? m RNA expression in AG were significantly decreased?p<0.01?.Compared with AG,the above results were significantly increased in AMG?p<0.01?.Compared with CG,the CD⁸⁺ in AG was significantly increased?p<0.01?.Compared with AG,the above results were significantly decreased in AMG?p<0.01?.The CD⁴⁺,IL-6 and IL-10 m RNA expression in MG rats increased significantly compared with CG?p<0.05,p<0.01?,indicating that MT can alleviate aluminum-induced inhibition of immune function in spleen.?3?Compared with CG,the levels of MDA and ROS in AG were significantly increased?p<0.01?.Compared with AG,the above results were significantly decreased in AMG?p<0.01?.Compared with CG,the activities of SOD and CAT in AG were significantly decreased?p<0.01?.Compared with AG,the above results were significantly increased in AMG?p<0.01?.The level of ROS in MG was significantly decreased compared with CG?p<0.01?,indicating that MT can alleviate aluminum-induced oxidative stress in the spleen.?4?Compared with CG,the apoptotic rate,Cyt-c protein expression,Capsase-3 and Capsase-9 m RNA expressions and activities,and Bax m RNA and protein expressions were significantly increased in AG?p<0.01?.Compared with AG,the above results were significantly decreased in AMG?p<0.01?.Compared with CG,the MMP and Bcl-2 m RNA and protein expressions in AG were significantly decreased?p<0.01?.Compared with AG,the above results in AMG were significantly increased?p<0.01?,indicating MT can inhibit aluminum-induced spleen apoptosis.?5?Compared with CG,the expressions of Nrf2 and Keap1 m RNA and protein and NQO1,HO-1,SOD1 and CAT m RNA in AG were significantly decreased?p<0.01?.Compared with AG,the above results were significantly increased in AMG?p<0.01?.m RNA and protein expression of Nrf2 in MG was significantly increased compared with CG?p<0.05?,indicating that MT can activate the Nrf2 signaling pathway inhibited by aluminum.Conclusion: MT can effectively alleviate aluminum-induced spleen structure damage and immunosuppression,which is related to resisting oxidative stress,blocking abnormal cell apoptosis and activating Nrf2 signaling pathway.