Study On Anti-Parkinson Disease Of Dietary Tryptophan Activating AhR Pathway

[Objective]To explore the effect of dietary tryptophan on rotenone-induced Parkinson's(PD)rats' motor symptoms,and to reveal its anti-PD mechanism of metabolizing intestinal flora to activate Ah R pathway to reduce neuroinflammation.[Methods]1.Rotenone(2mg / kg / d)was injected subcutaneously for 28 days to establish PD rat model.Then randomly divided into a control group(normal rats),PD group,PD + tryptophan deficiency group(without tryptophan in the feed)and PD + tryptophan group(with tryptophan in the feed),using open field test PD rat motor function,Westernblot detection of NF-k? nuclear translocation in rat substantia nigra,ELISA detection of proinflammatory cytokines IL-1?,IL-6,TNF-? levels in serum,to observe the anti-PD effect of tryptophan.2.In PD rats with dietary tryptophan diet,ampicillin(6mg / 20 g / d)was administered by gavage for 1 week and vancomycin(3mg / 20 g / d)by gavage for 1 week,and the open field was applied Experimental detection of PD motor function of rats,Western blot detection of NF-k?nuclear translocation in rat substantia nigra,ELISA detection of proinflammatory cytokines IL-1?,IL-6,TNF-? levels in serum,observation of tryptophan anti-PD Whether the effect is related to intestinal flora.3.PD rats in the dietary tryptophan group were treated with aromatic hydrocarbon receptor inhibitor CH223191,Western blotting was used to detect the expression of Ah R target gene CYP1B1 and NF-k? nuclear translocation in the substantia nigra of rats.For motor function,ELISA was used to detect the levels of proinflammatory cytokines IL-1?,IL-6and TNF-? in serum,and to observe whether the anti-PD effect of tryptophan depends on the Ah R pathway.[Results]1.Tryptophan has anti-PD effect: dietary tryptophan can improve rotenone-induced PD Behavioral scores of model rats.Westernblot showed increased NF-k B nuclear translocation in the substantia nigra and decreased the levels of proinflammatory cytokines IL-1?,IL-6 and TNF-? in the serum of PD model rats.2.The anti-PD effect of tryptophan depends on the intestinal flora:PD rats in each tryptophan group were treated with ampicillin(which can clear the intestinal tryptophan metabolism flora),and dietary tryptophan improved the PD model rats Behavioral score,Westernblot showed increased NF-k B nuclear translocation in the substantia nigra,serum proinflammatory cytokines IL-1?,IL-6,TNF-? levels increased,but vancomycin intervention did not have the above effect.3.The anti-PD effect of tryptophan intestinal microbial metabolites depends on the Ah R pathway: dietary tryptophan can upregulate the expression of CYP1B1 in the substantia nigra of PD rats and inhibit the nuclear translocation of NF-k B in substantia nigra.After intervention with the aromatic hydrocarbon receptor inhibitor CH223191,dietary tryptophan improved the behavioral scores of PD model rats.Westernblot showed increased NF-k B nuclear translocation in the substantia nigra and serum proinflammatory cytokines IL-1?,IL-6,TNF-? levels increase.[Conclusion]Tryptophan metabolites improves neuroinflammation and antagonizes Parkinson's disease by activating AHR pathway through intestinal flora metabolism.