Study on the mechanism of Sishen Pills in treating chronic ulcerative colitis based on transcriptomics
Objective:To analyze the mechanism of Sishen Pills in the treatment of ulcerative colitis(UC)based on transcriptomics.Methods:Eighteen of 108 SPF male C57BU6 mice were randomly selected as blank group(group K),and the other 90 mice were established with spleen and kidney yang deficiency UC model by disease and syndrome modeling method.After the establishment of the UC model of spleen-kidney yang deficiency,they were randomly divided into model group(group M),Sishen Pills high-dose,medium-dose and low-dose groups(groups G,Z and D)and Mesalazine positive control group(group Y),with 18 individuals/group.Groups K and M were given distilled water by intragastric administration,and each treatment group was given corresponding drugs and doses by intragastric administration for 21 consecutive days.The general state of mice in each group was observed,and the pathological changes of colonic mucosa were observed by HE staining.Transcriptomic sequencing technology was used to detect the gene expression profiles of colon tissues of mice in groups K,M and G,and the significantly differentially expressed genes were annotated into gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis;Western Blot and RT-qPCR were used to detect the expression of transient receptor potential vanilloid 1(TRPV1)and transient receptor potential melastatin 8(TRPM8)proteins and genes in mouse colon tissues,respectively.Results:Compared with group K,the general state of mice in group M was poor,and the colon tissue was severely damaged.Compared with group M,the general state and colon tissue damage of mice in groups G,Z,D and Y were improved to varying degrees,among which group G,Z and D,group G showed the most obvious improvement.Transcriptomic analysis showed that the K vs.M and M vs.G differential genes were widely involved in taste transduction,olfactory transduction,the regulation of TRP channels by inflammatory mediators and the interaction between cytokines and cytokine receptors,and were mainly involved in biological processes in response to temperature stimulation.Western Blot and RT-qPCR results showed that compared with group K,the expression levels of TRPV1 protein and mRNA in colon tissue of mice in group M were significantly decreased(P＜0.01),while the expression levels of TRPM8 protein and mNRA were significantly increased(P＜0.01).The expression levels of TRPV1 protein and mRNA in colon tissue of mice in group G were significantly increased(P＜0.01),and the expression levels of TRPM8 protein and mRNA were significantly decreased(P＜0.01).Conclusion:Sishen Pills may regulate the expression of TRP channel-related proteins and genes,repair the damaged colonic mucosal tissue,and achieve the purpose of treating UC.
Sishen PillsUlcerative colitis(UC)Spleen and kidney yang deficiencyTranscriptomicsTRP channel
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