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Clinical And Experimental Study On The Effect Of Banxia Xiexin Granule On Intestinal Flora And Intestinal Barrier In Type 2 Diabetes Mellitus Based On "intestinal Microflora-host" Interaction Model

Posted on:2020-02-23Degree:DoctorType:Dissertation
Country:ChinaCandidate:L L MaoFull Text:PDF
GTID:1364330647461550Subject:Chinese medical science
Abstract/Summary:PDF Full Text Request
【Objective】Based on the interaction of"intestinal flora-host",the effect of Banxia Xiexin Granules on intestinal flora and intestinal mucosal barrier function in type 2 diabetes mellitus was observed with the method of invigorating spleen and dispersing essence as theoretical index,in order to increase the application scope of Banxia Xiexin Granules.At the same time,through clinical and basic experiments,to verify the effectiveness of traditional Chinese medicine on regulating intestinal flora and improving glucose metabolism.【Methods】Blood glucose,insulin resistance,immune response,intestinal barrier and intestinal flora were detected in patients and rats using clinical trials and basic tests.In clinical trials,70 patients with type 2 diabetes were randomly divided into control group(group A,n=35)and Banxia Xiexin Granule treatment group(group B,n=35).The original insulin treatment scheme was maintained.In group A,Banxia Xiexin Granule simulation agent(placebo)was given,and in group B,Banxia Xiexin Granule was given,all of which were 10 g/times,three times a day,after 100ml fresh warm water was taked,treatment for 12 weeks.Fasting blood glucose,insulin,immune response factor and intestinal flora were detected before and after the intervention.In the basic experiment,120 SPF-class SD male rats were screened,which was about 200±20 g weight,and the temperature of the animal house was 22°C±2°C,and the humidity was 26%-30%,10 in the control group NG and 110 in the DM module.The rats were fed a high-fat and high-sugar diet for 15 days,then stop feeding for half a day,the intraperitoneal injection of 35mg·kg-1STZ was performed for 2 times.After the completion of the model,the rats were fed with ordinary feed.After 3 days,under the conditions of fasting,the blood sugar 16.7~30.0mmol·L-1was selected by the method of tail-cutting.The diet and stool of some rats have changed.Among them,50 rats meet the requirements,which are grouped as follows.DM was the model group,DM-MET was the metformin group(0.16g·kg-1),DM-HD(13.96g·kg-1)was the high-dose group of Banxia Xiexin Granules,DM-MD(6.98 g·kg-1)was medium-dose group of Banxia Xiexin Granules,DM-LD was low-dose group of Banxia Xiexin Granules(3.49g·kg-1),and the other groups were given the same volume of normal saline for four weeks.The day before the material was taken,the feces of rats were collected by forced method.For the detection of intestinal flora structure,the16s DNA method was mainly selected.After the extraction,the immune response factors and intestinal barrier were determined.【Results】Clinical Trials:(1)After treatment,compared with group A,the P values??of FPG,P2h PG and HOMA-IR in group B were less than 0.05(P<0.05),and the P values??of Hb A1c and HOMA-βwere less than 0.05(P<0.05).Statistically significant;(2)After treatment,compared with group A,the difference of LPS,IL-6 and TNF-αin group B was statistically significant(P<0.05);(3)After treatment,compared with group A,the difference of DAO in group B was statistically significant(P<0.05);(4)The results of 16s DNA showed that after treatment,compared with group A,the proportion of Firmicutes and Bacteroidetes was increased at the level of the group B,and Clostridia and Bacteroides were at the level of the group.The proportion of Bacteroidia decreased,and the proportion of Closteidiales and Bacteroidale decreased at the target level,and the proportion of Bacteriodaceae and Ruminococcaceae increased at the family level.In general,Banxia Xiexin Granules can regulate the composition of intestinal microbes,inhibit the formation of pathogenic bacteria,and promote the proliferation of probiotics.Basic test:(1)Compared with NG,STZ-induced DM rats had significantly higher body weight and FPG levels(P<0.05);HOMA-IR and HOMA-βlevels were significantly lower(P<0.05);compared with DM,Pinellia Xiexin Granules can reduce body weight and FPG levels,and increase HOMA-IR and HOMA-β(P<0.05);(2)Compared with NG,the LPS,IL-6,TNF-α,TLR-4,and NF-ΚB in DM rats were significantly increased(P<0.05);compared with DM,Banxia Xiexin Granules can reduce the expression level of immune response factors(P<0.05);(3)Compared with NG,ZO-1 and occludin were significantly decreased in DM rats,which was statistical difference(P<0.05),DAO was significantly increased,and there was statistical difference(P<0.05);In contrast,Banxia Xiexin Granules can repair ZO-1 and occludin proteins(P<0.05)and reduce DAO blood transfusion rate(P<0.05).(4)The results of 16s DNA showed that compared with NG,DM showed a certain degree of decrease in the level of the door,showing a certain degree of improvement,and a certain degree of proportion increased at the level of the level,showing a certain degree of proportion.At a certain level,the proportion of the target increased,and the proportion decreased.At the family level,Muribaculaceae,Lachnospiraceae increased,and Lactobacillaceae decreased.Compared with DM,Banxia Xiexin Granules can effectively improve the intestinal flora status.It has an excellent regulation effect on the ratio of Bacteroides/Thickwall bacteria.【Conclusion】(1)Both type 2 diabetic patients and rats treated with Banxia Xiexin Granules showed a decrease in blood glucose and a decrease in insulin resistance index;(2)The levels of IL-6 and TNF-αwere decreased in type 2 diabetic patients and rats treated with Banxia Xiexin Granules,and the immune response balance of intestinal mucosa was adjusted and the immune barrier function was strengthened;In animal experiments,supplemental detection of intestinal mucosal physical and chemical barrier indicators difficult to detect in human experiments,verifying the efficacy of Banxia Xiexin Granules;(3)In clinical and animal experiments,Banxia Xiexin Granules showed a regulatory effect on intestinal microbial composition and promoted the proliferation of probiotics.13The two groups of experiments together proved that Banxia Xiexin Granules promoted the repair of intestinal tissue damage caused by type 2 diabetes,inhibited the production of endotoxin,and reduced the damage of intestinal flora to the physical and chemical barrier of intestinal mucosa.
Keywords/Search Tags:Type 2 diabetes mellitus, Intestinal flora, Banxia Xiexin granule, Mucosal barrie
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