Combined effects of Emodin and Geniposide on intestinal mucosal barrier damage and inflammatory response in rats with systemic inflammatory response syndrome
Objective To observe the protective and anti-inflammatory effects of Emodin and Geniposide compatibility on the intestinal mucosal barrier function damage in rats with systemic inflammatory response syndrome(SIRS).Methods Male Sprague-Dawley(SD)rats aged 6-8 weeks were randomly divided into normal control group,model group,Emodin group,Geniposide group,Emodin and Geniposide compatibility group(compatibility group),and Ulinastatin group.The SIRS model in rats was established by abdominal injection of yeast polysaccharide.The Emodin,Geniposide,Ulinastatin,and compatibility groups received administration immediately and 12 hours after the injection of yeast polysaccharide.After 24 hours of modeling,the contents of D-lactate(D-LA),diamine oxidase(DAO),endotoxin(ET),tumor necrosis factor-α(TNF-α),interleukins(IL-1β,IL-6,IL-10)in the serum of each group were measured;The small intestine was taken for histopathological examination,and the positive protein expression levels of nuclear factor-κB p65(NF-κB p65)and Toll-like receptor 4(TLR-4)in the small intestine tissue were determined by immuno histochemistry.Results Compared with the normal control group,the levels of D-LA,DAO,ET,TNF-α,IL-1β,IL-6 and IL-10 in the serum of the model group were significantly increased[D-LA(μmol/L):99.11±11.93 vs.36.94±1.92,DAO(U/L):5 018.80±759.00 vs.2 253.23±372.40,ET(μg/L):0.36±0.04 vs.0.15±0.02,TNF-α(ng/L):66.61±20.88 vs.9.47±0.78,IL-1β(ng/L):63.73±7.64 vs.25.86±5.90,IL-6(ng/L):392.00±56.47 vs.111.17±36.22,IL-10(ng/L):41.90±8.12 vs.19.75±1.54,all P<0.05],histopathological observations showed that the small intestine mucosa was significantly swollen,the arrangement of mucosal epithelial cells was disordered,and there was cell shedding,increased infiltration of inflammatory cells in the intestinal mucosa,decreased goblet cells,loose and congested lamina propria;the positive protein expression of TLR-4 and NF-κB in the small intestine tissue was enhanced[TLR-4 positive protein expression(A value):0.59±0.08 vs.0.27±0.04,NF-κB positive protein expression(A value):0.65±0.07 vs.0.30±0.06,both P<0.05].Compared with the model group,the levels of D-LA,DAO,and ET in the serum of the Emodin group,Geniposide group,Ulinastatin group,and compatibility group were significantly decreased[D-LA(μmol/L):67.49±8.32,69.08±6.76,69.17±5.63,58.16±7.12 vs.99.11±11.93,DAO(U/L):3 659.38±563.90,3 713.29±354.70,3 575.30±444.4,3 087.01±227.50 vs.5 018.80±759.0,ET(μg/L):0.27±0.04,0.24±0.03,0.23±0.03,0.20±0.02 vs.0.36±0.04,all P<0.05],and the contents of pro-inflammatory factors TNF-α,IL-1β,and IL-6 were significantly decreased[TNF-α(ng/L):44.34±10.63,39.23±11.74,35.80±11.49,28.74±9.56 vs.66.61±20.88,IL-1β(ng/L):50.30±8.22,46.74±5.10,48.25±5.16,40.84±5.02 vs.63.73±7.64,IL-6(ng/L):299.27±50.65,263.98±37.62,281.84±63.24,216.72±38.90 vs.392.00±56.47,all P<0.05].The levels of serum anti-inflammatory factor IL-10 were significantly increased(ng/L:92.63±32.83,87.34±30.79,71.66±16.82,133.70±39.40 vs.41.90±8.12,all P<0.05).The pathological changes in the intestinal tissue of the Emodin group,Geniposide group,compatibility group,and Ulinastatin group were reduced,and the positive expressions of NF-κB p65 and TLR-4 proteins in the small intestine tissue were significantly decreased[TLR-4 positive protein expression(A value):0.49±0.03,0.47±0.08,0.36±0.08,0.42±0.06 vs.0.59±0.08,NF-κB p65 positive protein expression(A value):0.50±0.06,0.49±0.07,0.42±0.06,0.46±0.09 vs.0.65±0.07,all P<0.05].Compared with the Emodin group and Geniposide group,the serum D-LA,DAO,ET,TNF-α,IL-1β,and IL-6 in the compatibility group were significantly decreased,the serum IL-10 level was significantly increased,the pathological changes in the intestinal tissue were reduced,and the expression levels of NF-κB p65 and TLR-4 in the small intestine tissue were significantly decreased(all P<0.05).Conclusions Emodin and Geniposide can help relieve SIRS induced by yeast polysaccharide,and their effect is related to protecting the intestinal mucosal barrier and inhibiting the inflammatory response.When combined,they exhibit a synergistic effect.
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