Study On The Effect And Mechanism Of Lactobacillus Plantarum LP33 On Alleviating Lead Toxicity In SD Rats

Lead(Pb)exposure is a considerable public health crisis worldwide.Pb is a recognized toxic heavy metal that is non-degradable in the environment and is still strongly absorbed by the soil and further concentrated in the food chain.Pb can accumulate in most tissues of mammals and cause irreversible damage and lesions.Traditional chelator therapies have too many side effects,and they have defects in safety and effectiveness.Lactic acid bacteria(LAB)are recognized as safe food-grade microorganisms and are widely used in the food industry.The development of LAB to relieve Pb poisoning is expected to become a new adjuvant treatment.Therefore,this project screened LAB with the potential to alleviate Pb toxicity;verified its function through animal models and studied its mechanism of action.By digging deeper into the new probiotic effects of LAB,we look forward to discovering new and more valuable probiotics and developing new strategies to treat or prevent Pb poisoning.The main findings are as follows:1.By studying the Pb adsorption,anti-oxidation,and tolerance to simulated gastrointestinal environment of 37 LAB,it was found that the Pb removal rate of Lactobacillus plantarum LP33(LP33)was the highest under different initial Pb concentrations(50 mg/L and 500 mg/L),which were 55.63% and 26.62%,respectively.LP33 showed good antioxidant capacity in the determination of DPPH scavenging rate,hydroxyl radical scavenging rate,and reducing ability.In addition,the strain also has good gastrointestinal tolerance,and its survival rates in artificial gastric juice and 0.3%bile salts are 104.08% and 20.86%,respectively.Taken together,LP33 has the potential to alleviate Pb poisoning.In addition,we have further proved that LP33 has Pb adsorption capacity through transmission electron microscopy,scanning electron microscopy,and energy dispersive X-ray spectroscopy.2.By establishing a rat model of Pb exposure,it was found that LP33 can significantly reduce blood Pb levels,significantly increase fecal Pb content,and significantly increase liver bile acid(BA)and fecal BA in Pb-exposed rats.Through further research,we found that LP33 up-regulated the expression of Cyp7a1,Cyp8b1,Bsep and Mrp2,down-regulated the expression of Fxr,Shp and Fgfr4,and enhanced liver BA synthesis and secretion.The strain also significantly inhibited the expression of Fxr,Fgf15,Asbt and OST? in the ileum,and inhibited the reabsorption of ileal BA.In general,by inhibiting the Fxr-Fgf15 axis,LP33 can promote the liver synthesis of BA and inhibit the reabsorption of Pb by the ileum,thereby blocking the enterohepatic circulation of Pb and BA,and increasing the excretion of lead in feces.3.LP33 can alleviate lead poisoning damage in SD rats.Compared with Pb-exposed rats,supplementing LP33 significantly increased the weight lost due to Pb exposure,at the same time restored the changes in oxidative stress-related indicators caused by Pb exposure,and reduced liver and kidney injury indicators levels,such as:AST,ALT,ALT,CRE and BUN,and reduced the histopathological damage caused by Pb exposure,also significantly reduced the levels of serum proinflammatory cytokines TNF-?,IL-1? and IL-6,and increased the anti-inflammatory cytokine IL-10 serum levels.It was further discovered that LP33 can promote the phosphorylation of AMPK and AKT,and then activate Nrf2,promote its nuclear translocation,and induce m RNA expression of its downstream antioxidant enzymes NQO1,HO-1,SOD1,SOD2 and CAT.In addition,the strain can significantly promote the expression of I?B?,inhibit the nuclear translocation of NF-?B,and then down-regulate the m RNA expression levels of the pro-inflammatory factors TNF-?,IL-1?,and IL-6,and up-regulate the anti-inflammatory cytokine IL-10 m RNA expression level.Overall,LP33 can alleviate lead toxicity by promoting the activation of the AMPK/AKT/Nrf2 pathway and inhibiting the NF-?B pathway.