Study On The Efficacy And Mechanism Of Lycium Barbarum Polysaccharide Against Lead-induced Renal Injury In Mice

At present,lead exposure and lead poisoning remain a growing public health problem in both developing and developed countries.The kidney was one of the most important organs for lead accumulation and one of the main target organs of lead toxicity.At present,significant progress has been made in the treatment of heavy metal nephrotoxicity with chelating agents,but the treatment with chelating agents has also been proved to have certain toxic side effects.Therefore,it has become a research hotspot at home and abroad to find effective,low-toxic,and low-side effects natural medicines to interfere with lead-induced kidney injury.Lycium barbarum polysaccharide（LBP）is a class of polysaccharide compounds obtained from the mature fruit of Lycium barbarum L.by extraction and purification,with multiple pharmacological effects such as anti-tumor,antioxidant,and kidney protection.The research group screened the anti-lead-induced kidney injury activity of common medicinal and edible plant polysaccharides in the early stage and found that Lycium barbarum polysaccharide has a significant anti-lead-induced kidney injury effect.However,the pharmacodynamic research of Lycium barbarum polysaccharide against lead-induced renal injury still needs to be further studied,and the"dose-effect"relationship and mechanism of its efficacy are still unclear.Therefore,the study on the efficacy and mechanism of LBP against lead-induced kidney injury has good research value and application prospects,which can provide new directions and ideas for the in-depth exploitation of LBP and the development of new natural drugs against lead-derived kidney injury.In this context,this thesis proposes to investigate the efficacy and mechanism of LBP against lead-induced kidney injury at low(200 mg·kg^-1),medium(400 mg·kg^-1),and high(600 mg·kg^-1)doses.Finally,the molecular mechanism of LBP against lead-induced kidney injury was further investigated based on the Nuclear factor E2 related factor 2（Nrf2）signaling pathway.The results are expected to provide theoretical support for the in-depth exploitation of LBP and the development of novel natural anti-Lead-induced kidney injury drugs.The main elements and results are as follows:1.Pharmacodynamic evaluation resultsFifty male ICR mice were randomly divided into five groups:blank group,model group,LBP low dose group,LBP medium-dose group,and LBP high dose group.A mouse model of lead-induced renal injury was established.The efficacy of low(200 mg·kg^-1),medium(400 mg·kg^-1),and high(600 mg·kg^-1)doses of LBP against lead-induced renal injury was evaluated by analyzing the feed intake,body weight and growth trend,kidney index,kidney histopathological sections,and renal function indicators such as the expression levels of Blood urea nitrogen（BUN）and Creatinine（Cre）.The results showed that LBP could significantly increase the food intake and body weight of mice with lead toxicity nephrogenic injury,promote the growth of mice,and significantly down-regulate the renal index and expression levels of BUN and Cre in mice with lead toxicity.Finally,the dose-effect of LBP against lead-derived kidney injury was analyzed by feeding,body weight,growth trend,kidney index,kidney histopathology section,and kidney function index of mice.2.Mechanism of Lycium barbarum polysaccharide against lead-induced kidney injury based on traditional targetsTo investigate the mechanism of LBP against lead-induced kidney injury,the expression levels of the traditional oxidative stress targets（Superoxide dismutase,SOD;Malondialdehyde,MDA;Glutathione S-transferase,GST;Glutathione,GSH）,inflammatory targets（Tumor necrosis factor-α,TNF-α;Interleukin-1β,IL-1β;Nitric oxide,NO）,and apoptotic targets（Caspase-3,Casp-3;Bcl-2-associated X protein,Bax;B-cell lymphoma-2,Bcl-2）were analyzed in each group of mice.The results showed that low,medium and high doses of LBP significantly reduce the oxidative stress,inflammation,and apoptotic responses in the kidney tissues of lead-toxic mice,with the medium dose of LBP having the most significant effect.3.Mechanism of Lycium barbarum polysaccharide against lead-induced kidney injury based on Nrf2 signaling pathwayTo investigate the molecular mechanism of LBP against lead-derived kidney injury,the mechanism of LBP against lead-derived kidney injury was investigated based on the Nrf2 signaling pathway.The results showed that low,medium,and high doses of LBP could promote the activation of the Nrf2 signaling pathway by down-regulating the expression of Keap1,promoting the production of antioxidants in kidney tissues,and reducing the oxidative stress,inflammation,and apoptosis responses in kidney tissues.