Effect and Mechanism of Optimized Kuijie Decoction in Ulcerative Colitis Rats with TCM Syndrome Differentiation of Qi Stagnation and Blood Stasis

Abstract

Background Experiential effective prescription optimized Kuijie decoction can effectively improve the quality of life of patients with ulcerative colitis (UC), promote the intestinal mucosal healing and clinical remission, but its mechanism remains unclear now. Objective To investigate the effect and mechanism of optimized Kuijie decoction in UC rats with TCM syndrome differentiation of Qi stagnation and blood stasis. Methods From September to October 2023, 70 SPF-grade male SD rats were randomly divided into the blank-control, model, salicylazosulfapyridine, low-dose, standard-dose, Qi-enhancing and Blood-activating groups, with 10 rats in each group. UC model with TCM syndrome differentiation of Qi stagnation and blood stasis was established by trinitrobenzenesulfonic acid (TNBS) /ethanol secondary inflammation combined with restraint method. Rats in the blank-control group were enucleated with 0.9% sodium chloride solution at the time of modeling and were grasped and fixed synchronously with the rats in the other groups, and were given an equal volume of water by gavage once per day after the establishing for 14 days; rats in the model group were given an equal volume of water by gavage once per day after the establishing for 14 days; rats in the salicylazosulfapyridine, low-dose, standard-dose, Qi-enhancing and Blood-activating groups were given intragastric administration with salicylazosulfapyridine suspension (0.54 g/kg), low-dose optimized Kuijie decoction (0.837 g/kg), standard-dose optimized Kuijie decoction (1.674 g/kg), Astragalus suspension (1.8 g/kg) and Safflower suspension (0.9 g/kg) once per day after the establishing for 14 days, respectively. High-precision transmission electron microscope was used to observe the ultrastructural changes in the colonic tissues of the seven groups of rats after intervention, the expression levels of CXCR4, VEGFA, and TAK1 were compared among the seven groups of rats after intervention. Results The ultrastructure of colonic tissue of rats in the low-dose and standard-dose groups tended to be normal after intervention. The gray ratios of proteins and relative mRNA expression quality of CXCR4, VEGFA and TAK1 in colonic tissues of rats in the model group were higher than the blank-control after intervention (P<0.05) ; the gray ratios of proteins and relative mRNA expression quality of CXCR4, VEGFA and TAK1 in the salicylazosulfapyridine, low-dose, standard-dose, Qi-enhancing and Blood-activating groups were significantly lower than those in the model group (P<0.05) ; the gray ratios of proteins of CXCR4, VEGFA and TAK1 in the standard-dose group were significantly lower than those in the salicylazosulfapyridine group, relative mRNA expression quality of VEGFA and TAK1 in the Blood-activating group was significantly lower than that in the salicylazosulfapyridine group, respectively (P<0.05) . Conclusion Optimized Kuijie decoction and its Qi-enhancing and Blood-activating components can effectively reduce the expression of CXCR4, VEGFA and TAK1 in colonic tissue in UC rats with TCM syndrome differentiation of Qi stagnation and blood stasis, its therapeutic effect may act through the coordinate regulating of the expression of CXCR4, VEGFA and TAK1 in colonic tissue by Qi-enhancing component and blood-activating component.

Keywords

• colitis, ulcerative|syndrome of blood stasis and qi stagnation|rats|optimized kuijie decoction|molecular mechanisms of pharmacological action (tcd)