| Objective: The purpose of the study was to investigate the effects of Lanyinfengyanghuazhuojiedu Decoction on ulcerative colitis model rats through observing the general condition, disease activity index(DAI) scores and the m RNA expression changes of DOR, beta arrestin1 and Bcl-2 in the colon tissue,and then, try to further explore the effect of DOR-β-arrestin1- Bcl-2 signal transduction pathway in the pathogenesis of UC and the mechanism of Lanyinfengyanghuazhuojiedu Decoction by intervening the pathway.Methods: 60 eight-week-old male Wistar rats were randomly divided into six groups, each group 10 rats. They were respectively marked for the normal group(NG), model group(MG), high dose group(HDG), medium dose group(MDG), low dose group of Lanyinfengyanghuozhuo Jiedu Decoction(LDG) and the SASP group(SASP). The rats in NG was fed normally, the others in rest groups were induced with trinitrobenzene sulfonic acid /ethanol(TNBS/ethanol) in order to make UC animal models. After 4 days modeling, the NG continued to feed, the MG were given normal saline, the four treatment groups received corresponding drug gavage. After 2 weeks continuous treatment, observate the rats, the general condition including Mental state, body weight, stool consistency and the colonic mucosa general concept and histopathological changes. Detected the m RNA expression changes of DOR, beta arrestin1 and Bcl-2 in the colon tissue by Real Time-PCR and analyse effects of Lanyinfengyanghuazhuojiedu Decoction on the m RNA expression changes of these indicators.Results:1 The general state and DAI scoresCompared with the NG,the general condition of rats in other groups became lacking of energy, activity reduced, reaction decreased, yellowish dull fur, eating less, weight loss, diarrhea or bloody mucus. After the 14 days of dosing, the general condition of all rats in each group had varying degrees of improvement, in which the HDG was close to the NG. The general condition including Mental state, activity, stool consistency almost recovered to normal.While the condition of the MDG and SASP were slightly lower than the HDG, and there were no significant difference between the MDG and SASP,the LDG were better than the MG but less than the MDG and SASP, the recovery of the MG was the worst.The DAI scores:The HDG(0.37±0.35),MDG(0.81±0.29),LDG(1.56±0.41),SASP(0.78±0.29)compared with the MG(2.46±0.43)(P <0.05),the differences were statistically significant(P< 0.05);The MDG, LDG, SASP compared with the HDG,the differences were statistically significant(P <0.05);The MDG, SASP compared with the LDG,the differences were statistically significant(P<0.05); there was no statistically significant difference between the MDG and SASP(P >0.05).2 The general observation of colonic mucosa and the histopathological conceptThe general observation of colonic mucosa : the HDG was closely to the NG. The MDG and SASP were slightly worse than the HDG but better than the LDG, which had no significant difference between the two groups. The LDG was between the MDG and MG, the MG was the worst.The histopathologic aspects: Compared with the NG,which had the normal rat colon mucosa, plenty inflammatory cell infiltration, glandular structures change, goblet cell decrease,congestion and edema, erosion and ulcer formation were visible in the MG. The condition of colon mucosa in the HDG was close to the NG, The recovery condition of the SASP,MDG and LDG lay between the HDG and MG, while the MDG and SASP were better than the LDG.3 The expression of DOR, β-arrestin1 and Bcl-2m RNA in the experimental rat colon tissueDOR: Compared with the NG(0.3266±0.0168), the expression of DOR m RNA was significantly increased(P<0.05) in the MG(0.5319±0.0238). After the drug treatment, compared with the MG, the expression of DOR m RNA was significantly decreased(P<0.05) in the four treatment groups. The HDG( 0.3473±0.0110) compared with the MDG( 0.3914±0.0245), LDG(0.4515±0.0209)and SASP(0.3733±0.0191), significant difference can still be observed(P<0.05), while the MDG and SASP compared with the LDG, statistically significant difference(P<0.05), the MDG compared with the SASP, no statistically significant difference( P>0.05).β-arrestin1:Compared with the NG(0.3209±0.0186), the expression of β-arrestin1 m RNA was significantly increased(P<0.05) in the MG(0.5217±0.0215). After the drug treatment, compared with the MG, the expression of β-arrestin1 m RNA was significantly decreased(P<0.05)in the four treatment groups. The HDG(0.3443±0.0141)compared with the MDG(0.4052±0.0289), LDG(0.4535±0.0269)and SASP(0.3941±0.0256), significant difference can still be observed(P<0.05), while the MDG and SASP compared with the LDG, statistically significant difference(P<0.05), the MDG compared with the SASP, no statistically significant difference( P>0.05).Bcl-2:Compared with the NG(0.3217±0.0230), the expression of Bcl-2m RNA was significantly increased(P<0.05) in the MG(0.5256±0.0273). After the drug treatment, compared with the MG, the expression of Bcl-2 m RNA was significantly decreased(P<0.05) in the four treatment groups. There was no statistically significant difference(P>0.05) between the HDG(0.3350±0.0142)and the NG, while the treatment groups compared with the MG, significant difference(P<0.05) was obvious. The HDG compared with the MDG( 0.3797±0.0230), LDG( 0.4349±0.0203) and SASP(0.3573±0.0106), significant difference can still be observed(P<0.05), while the MDG and SASP compared with the LDG, statistically significant difference(P<0.05), the MDG compared with the SASP, statistically significant difference( P<0.05).Conclusion:1 Lanyinfengyanghuazhuojiedu Decoction not only can improve the general state of UC rats including diarrhea, mucous pus etc, but also well promote the injured healing of colonic mucosa and showing a certain amount-effect relationship, large dose group is better than medium and low dose group.2 The mechanism of Lanyinfengyanghuazhuojiedu Decoction on the treatment of UC may be by interfering the activation step of DOR-β-arrestin1-Bcl-2 signal transduction pathway, promoting t. lymphocytes cell apoptosis in the colonic mucosa, in order to achieve the immune homeostasis. |
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