Effects Of The Dosage And The Timing Of Panax Notoginseng Administration In The Treatment Of Colonic Microvascular Injury In UC Rats

Objective:This study focused on the effects of the dosage and the timing of Panax notoginseng administration in order to explore the optimal time and dosage of Panax notoginseng in treatment of UC.Meanwhile,we explore the mechansim of Panax notoginseng on repair of colonic mucosal mircovascular injury to clarify the modern scientific connotation of traditional Chinese medicine for promoting blood circulation and removing blood stasis,and provide data for further study and clinical practice.Methods:Part I:The SD rats were divided into control,IA model,DSS model groups,and the groups treated with low,mid and high doses of PN.UC models:the rats were induced by IA and 5%DSS solution respectively.PN was intragastrically administered at the 3rd day after the model established at the dosages of 0.5g/kg,1.0g/kg and 2.0g/kg respectively for 7 days.HE staining was used to evaluate the severity of colonic mucosal and mirovascular injuries.The MVD was evaluated with immunohistochemistry,and the MVP was evaluated by Evans blue method.The serum concentrations of cytokines,including IL-6?TNF-??IL-4?IL-10?VEGFA165 and VEGFA121,were detected with ELISA kits.SOD and MPO activities were detected by SOD and MPO assay kits respectively.The expression of colonic HIF-1?protein was measured by western blot.Part II:SD rats were divided into control,IA model,DSS model and PN treatment groups.PN?1.0g/kg?was given at the 3^rdor 7^thday after the model established respectively.The severity of the colitis was evaluated with DAI,and the pathological lesions were observed under the microscope.The other detection indexes,including MVD,SOD,MPO,the serum contents of inflammation cytokines and the expression of HIF-1?protein,were measured as before.Results:Part I:Compared with control group,the DAI scores of UC rats was significantly decreased after PN treatment,meanwhile the colonic mucosal tissue damage and inflammatory cell infiltration were relived.Furthermore,the colonic microvessel density in the PN treatment groups were significantly increased,whose vascular permeability decreased.The results of ELISA showed that the levels of serum pro-inflammatory cytokines?IL-4 and IL-10?were markedly increased,and the ratio of VEGF165/VEGF121 was lower than that of the model group.Compared with the low-dose PN group,the levels of serum inflammatory cytokines in the middle-and high-dose PN groups were changed more obviously.Under microscope,the colonic inflammation and microvascular injury in the middle-and high-dose groups were lighter than those in the low-dose group.Meanwhile,the activity of SOD in the colonic and MVD were increased more than those in the low-dose group;the activity of MPO and MVP were decreased more than those in the low-dose group.The WB results showed that the expression of HIF-1?protein in the colon of middle-and high-dose groups was down-regulated and lower than that in the low-dose group.However,those changes mentioned above were not significantly different between the middle-dose and high-dose group.Part?:Compared with the rats on the 7^thday of modeling,the DAI scores of the rats in the early treatment group were evidently lower,and the colitis and microvascular injury in those rats were lighter.The activity of SOD and MVD in the rat colon were higher,while the activity of MPO and MVP were lower than those in the 7^thday administration group.Moreover,the contents of pro-inflammatory cytokines in the 3^rdday administration group obviously decreased,with the anti-inflammatory cytokines increased.Conclusions:Panax notoginseng can promote the repair of colonic mucosal microvascular injury and alleviate the colitis in UC rats induced by IA and DSS.The effect of Panax notoginseng is correlated with the dosage of Panax notoginseng,and the middle-dose may be the best dosage of Panax notoginseng for the treatment of UC.Besides,it is better to treat with Panax notoginseng at early stage of UC.Panax notoginseng can alleviate hypoxia in colon tissue,inhibit oxidative stress,and regulate the colon microangiogenesis,thereby promoting the repair of colonic microvascular damage.