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Interventional Effects And Mechanisms Of Lycopene On The Renal Injury In AFB1 Exposed Mice

Posted on:2020-02-10Degree:MasterType:Thesis
Country:ChinaCandidate:K Y YuFull Text:PDF
GTID:2393330575990024Subject:Clinical Veterinary Medicine
Abstract/Summary:PDF Full Text Request
Aflatoxin B1(AFB1),a common mycotoxin,can accumulate in the kidney and cause renal injury.Oxidative stress and apoptosis are important pathological mechanisms of AFB1-induced renal injury.Lycopene(LYC)has the renal protective effect,and can enhance renal antioxidant and antiapoptosis capacity.However,whether LYC can alleviate AFB 1-induced renal injury has not been reported.This study is theoretical foundation with LYC could intervene AFB1-induced renal injury,and male Kunming mice were selected as subjects.Firstly,the effects of concentration gradient AFB1 on kidney structure and function were studied,to select proper AFB1 exposure dosage.Secondly,80 mice were randomly divided into four groups: control group(CG),AFB 1 group,LYC intervention group(ALG)and LYC group(LG).Renal structure and function,oxidative stress state,the expression of key factors of apoptosis and Nrf2 signaling pathway were observed to evaluate the effect and mechanism of LYC on AFB1-induced renal injury.The results were shown as follows:(1)Compared with CG,the body weight,renal weight in AG were significantly decreased(p<0.01).Compared with AG,the body weight in ALG were decreased with no significant(p>0.05),renal weight were significantly decreased(p<0.01).Indicating that LYC can alleviate the growth retardation induced by AFB1 in mice.(2)In CG,the structure of kidney tubules,glomerulus and Bowman’s capsule are complete,the morphology and range of these cells were natural.In AG,there were severe histopathological changes,including glomerular atrophy,Bowman’s capsule epithelial cell hyperplasia,the shed and nuclei loss of kidney tubule epithelial cells,renal tubular cavity narrowing and blurring.In ALG,the pathological changes were significantly attenuated wh en compare with AG.In LG,the renal structure were normal compared to CG.In CG renal cellsubmorphological structure were natural,the morphology and structure of the nucleus and mitochondria were normal,the rough endoplasmic reticulum was abundant,and the cytoplasm was uniform.In AG,there were severe ultrastructural changes,including nucleus became smaller,membrane is unclea,the wollen and vacuolation and cristae partly disintegrated of mitochondrial,and ncreased lysosome.In ALG,the mitochondria l damage is decreased and the nuclear morphology returns to normal.In LG,the renal cell morphology were normal and were no significant difference when compared with CG.The results showed that LYC can alleviate AFB1-induced damage of renal structure.Compared with CG,the contents of BUN,SCR,NAG and β2-Mg in AG were significantly increased(p<0.01).Compared with AG,the contents of BUN,SCR,NAG and β2-Mg in ALG were significantly decreased(p<0.01).The results showed that LYC can alleviate AFB 1-induced damage of renal function.(3)Compared with CG,T-AOC and the contents of GSH,and the activity of SOD and CAT in AG were significantly decreased(p<0.01),the contents of MDA,H2O2,and ROS were significantly increased(p<0.01).Compared with AG,T-AOC and the contents of GSH,and the activity of SOD and CAT in ALG were significantly increased(p<0.01),the contents of MDA and H2O2 and ROS were significantly decreased(p<0.01).In LG mice kidney,T-AOC were significantly higher than those in CG(p<0.05),the contents of MDA were significantly lower than those in CG(p<0.05).The results showed that LYC can alleviate AFB1-induced renal oxidative stress.(4)In CG,renal cells and nuclear membrane are normal in appearance,nucleolus are clear.I n AG,there were severe apoptotic morphological features,including nuclear chromatin gathered and chromatolysm and nuclear membrane invaginates obscure.In ALG,cell nucleus were normal and the apoptotic morphological features were significantly decreased when compared with CG.Compared with CG,MMP and the protein expressions of Bcl-2 in AG were significantly significantly decreased(p<0.01),the protein expression of Cyt-c,Bax,Caspase-3 and Caspase-9,and the activity of Caspase-3 and Caspase-9,and Bax/Bcl-2 were significantly increased(p<0.01).Compared with AG,MMP and the protein expressions of Bcl-2 in ALG were significantly increased(p<0.01),the protein expression of Cyt-c,Bax,Caspase-3,Caspase-9,and the activity of Caspase-3 and Caspase-9,and Bax/Bcl-2 were significantly decreased(p<0.01).The results showed that LYC can alleviate AFB1-induced renal cell apoptosis.(5)Compared with CG,the m RNA expressions of Nrf2 in AG were significantly increased(p<0.05),the content of nuclear and cytosolic Nrf2 protein in AG were significantly decreased(p<0.05).Compared with AG,the m RNA and the protein content of Nrf2 in ALG were significantly increased(p<0.01).In LG,the m RNA and the protein content of Nrf2 were significantly higher than those in CG(p<0.01).Compared with CG,the m RNA and protein expressions of NQO1,CAT,SOD,GSS,GCLC and GCLM in AG were significantly decreased(p<0.05,p<0.01);the above results in ALG were significantly higher than those in AG(p<0.05,p<0.01);the above results in LG were significantly higher than those in CG(p<0.05,p<0.01).The results showed that LYC can alleviate the decrease of AFB1-exposed mice renal antioxidation capacity with the activation of Nrf2 signaling pathway.Conclusion: LYC can effectively alleviate AFB1 induced renal injury,and is related to alleviating oxidative stress,inhibiting apoptosis and activating Nrf2 signaling pathway.The results can provide theoretical basis and experimental basis for the release of AFB 1 nephrotoxicity.
Keywords/Search Tags:Lycopene, Aflatoxin B1, Mice nephrotoxicity, Oxidative stress and apoptosis, Nrf2
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