Regulatory effect of Dizhuo decoction on intestinal dysbiosis in hyperuricemic rats based on TLR4/NF-KB signaling pathway
Objective To observe the regulatory effect of Dizhuo decoction on intestinal dysbiosis in hyperuricemic rats via the TLR4/NF-κB signaling pathway.Methods Seventy SPF male rats were randomly divided into NC group,HUA group,DZTL group,DZTM group,DZTH group,positive control group,and DZTH+LPS group,with 10 rats in each group.The levels of serum uric acid(SUA),creatinine(Cr),blood urea nitrogen(BUN),xanthine oxidase(XOD)and en-dotoxin(LPS)in the sera of rats were detected.The pathological changes of kidney tissue were observed with HE staining.The α-diversity and community structure of intestinal flora were analyzed with 16S rDNA sequencing.The expressions of TLR4 and p-NF-κB p65 proteins in kidney tissue were detected using Western blot.Results Compared with the NC group,the levels of SUA,Cr,BUN,XOD and LPS in the serum of rats in the HUA group significantly increased(all P＜0.05).Compared with the HUA group,the levels of SUA,Cr,BUN,XOD and LPS in the sera of rats in the DZTL,DZTM,DZTH and positive control groups significantly decreased.The Shannon index,Sobs index,Chaol index and Ace index also significantly reduced,with the most significant changes observed in the DZTH and positive control groups(all P＜0.05).Compared with the DZTH group,the levels of SUA,Cr,BUN,XOD and LPS in the serum of rats in the DZTH+LPS group significantly increased,and the Shannon index,Sobs index,Chaol index and Ace index also signific-antly increased(all P＜0.05).Compared with the NC group,the relative abundances of Firmicutes,Actinomycetes,Clostridiaceae,Ruminococcaceae,Lactobacillaceae,Helicobacter and Bifidobacterium in the HUA group significantly re-duced,while those of Spirochaetaceae,Bacteroidetes,TM7,Prevotella,Bacillaceae and TM-3 significantly increased(all P＜0.05).Compared with the HUA group,the relative abundances of Firmicutes,Actinomycetes,Clostridiaceae,Rumino-coccaceae,Lactobacillaceae,Helicobacter and Bifidobacterium in the DZTL,DZTM,DZTH,and positive control groups significantly increased,while those of Spirochaetaceae,Bacteroidetes,TM7,Prevotella,Bacillaceae and TM-3 signific-antly reduced(all P＜0.05).Compared with the DZTH group,the relative abundances of Firmicutes,Actinomycetes,Clostridiaceae,Ruminococcaceae,Lactobacillaceae,Helicobacter and Bifidobacterium in the DZTH+LPS group signific-antly reduced,while those of Spirochaetaceae,Bacteroidetes,TM7,Prevotella,Bacillaceae and TM-3 significantly in-creased(all P＜0.05).Compared to the NC group,the expression of TLR4 and p-NF-κB p65 proteins in renal tissues in the HUA group rats significantly increased(P＜0.01).Compared to the HUA group,the expression of TLR4 and p-NF-κB p65 proteins in renal tissues in the DZTL,DZTM,DZTH and positive control groups significantly decreased(all P＜0.01).There were no statistically significant differences in the expression of TLR4 and p-NF-κB p65 proteins in renal tissues between the DZTH and positive control groups(P=0.559).Compared to the DZTH group,the expression of TLR4 and p-NF-κB p65 proteins in the DZTH+LPS group significantly increased(P＜0.01).Conclusion Dizhuo decoction can im-prove the balance of intestinal flora in rats with hyperuricemia,exerting an anti-hyperuricemia effect,and its mechanism of action is related to the inhibition of TLR4/NF-κB signaling pathway activation.
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