| Background and Objective:Acute pancreatitis(AP)is a common acute abdomen in the digestive system.Its incidence rate is increasing year by year.Patients with AP can develop intestinal dysfunction in the early stage of the disease,which leads to imbalance of intestinal flora,increase of intestinal mucosal permeability,and then translocation of intestinal flora,which increases the risk of enterogenous infection.At the same time,intestinal dysfunction is also an important predisposing factor for systemic inflammatory response syndrome(SIRS)and multiple organ dysfunction syndrome(MODS),which increases the mortality.Intestinal dysfunction mainly includes digestion and absorption disorders,secretion disorders,immune disorders,intestinal motility disorders and intestinal mucosal barrier disorders,among which mucosal barrier damage plays an important role in intestinal dysfunction.The intestinal mucosal barrier is mainly composed of a mechanical barrier,a chemical barrier,an immune barrier and a microbial barrier,of which the microbial barrier is mainly composed of the intestinal flora symbiotic with the human body.In the early stage of AP patients,there is an imbalance of intestinal flora,which damages the intestinal mucosal biological barrier,leading to intestinal mucosal barrier dysfunction and aggravating intestinal dysfunction in AP patients.Recovering intestinal function as soon as possible and regulating the imbalance of intestinal flora is the key to preventing the progression of AP and improving the prognosis,and it is also a hot spot of current scholars.Clinically,the traditional Chinese medicine rhubarb is widely used in patients with AP.Its efficacy in reducing the level of inflammatory response in patients,improving intestinal dysfunction and prognosis of AP patients has been confirmed in many studies.Some studies have shown that it can also regulate intestinal flora.However,in clinical application,rhubarb also has some problems,such as poor taste,which may aggravate patients’ nausea,vomiting and gastrointestinal burden,and its adverse effect on electrolyte balance.As a prebiotic,lactulose is an important microecological regulator on the one hand,and a high-permeability laxative on the other hand,which plays a good role in regulating intestinal flora and improving intestinal function.It has been widely used in clinical practice,but its therapeutic value in AP patients is still unclear.In this study,a randomized controlled study was conducted to compare the regulatory effects of large doses of lactulose and rhubarb on intestinal dysfunction and intestinal microflora imbalance in patients with mild and moderate severe acute pancreatitis complicated with intestinal dysfunction,and to clarify the therapeutic value of lactulose in AP.Method:The MAP and MSAP patients admitted to the Department of Gastroenterology of the First Affiliated Hospital of Nanchang University from December 2019 to December 2020 with intestinal dysfunction but no acute respiratory,renal and circulatory failure were included as the study subjects,and randomly assigned to the lactilose group or the rhubarb group.Laparlose group was combined with large dose of Laparlose(50ml,twice a day,orally)on the basis of conventional treatment,while rhubarb group was combined with rhubarb(50g raw rhubarb was added into 100 ml warm boiled water,twice a day,orally)on the basis of conventional treatment.The patients’ intestinal function(abdominal pain and distension,nausea and vomiting,gastrointestinal decompression,number of bowel noises,stool frequency,intestinal nutrition tolerance)and prognosis(infection rate,organ failure rate,ICU occupancy rate,length of stay,mortality rate,etc.)were observed and recorded daily during their hospitalization.We have counted the tolerance rate of total enteral nutrition on the 7th day after admission,the number of days for patients to recover from total enteral nutrition and the number of days for patients’ score of intestinal dysfunction(SGD)to return to0.Serum and fresh stool samples were collected within 24 hours after admission and on the 7th day after treatment,and frozen in the refrigerator at-80 ℃.Enzyme-linked immunosorbent assay was used to measure the indicators of intestinal mucosal barrier injury(DAO,D-Lac)and inflammatory factors(TNF-α,IL-1β,CRP,PCT)level.16 Sr RNA high-throughput sequencing was used to analyze the structure of intestinal flora in two groups before and after treatment.Short-chain fattyacids(SCFAs)in intestinal tract were determined by gas chromatography-mass spectrometry(GC-MS).Fast-fed fecal samples of 28 healthy subjects were collected as reference.The follow-up period was 3 months.SPSS25.0 software and Meji biological cloud platform were used for data statistical analysis.Result:A total of 73 patients were enrolled during the study period,including 36 in the lactulose group and 37 in the rhubarb group.There were no significant differences in baseline data between the two groups,such as gender,age,duration of onset and admission,etiology,and severity scores at admission(APACHE II score,SIRS score,modified Marshall score,and modified CT severity index score).There was no significant difference between the two treatment groups in the indicators reflecting the recovery of intestinal function,such as the tolerance rate of total enteral nutrition on the 7th day of admission,the days of recovery ability to receive total enteral nutrition,and the days of SGD score returning to 0(the tolerance rate of total enteral nutrition on the 7th day of admission was 72% in the lactose group and 69% in the rhubarb group,P =0.592;The days of recovery tolerance to total enteral nutrition were6.2±2.06 in lactilose group and 6.6±1.84 in rhubarb group,P =0.298;The number of days when SGD score returned to 0:6.55±2.24 days in lactilose group and 7.25±12.04 days in rhubarb group,P =0.592).There were no significant differences in the indicators of prognosis between the two groups(total infection rate was 25% and 27%,P =0.564;The incidence of organ failure was 19.4% and 16.2%,P =0.869;The rates of minimally invasive intervention were 13.8% and 11.8%,P =0.758;Mean total hospitalization days were 9.06 and 10.32,P =0.279).One patient in each group was transferred to the ICU,and there was no death.D-LAC,TNF-α,IL-6,CRP,PCT and other serum indexes in two groups were significantly decreased after treatment(P <0.05),and the decrease rates of IL-6,TNF-α and D-LAC in lactulose group were significantly higher than those in rhubarb group after treatment(IL-6: P=0.019;TNF alpha p = 0.015;D-LAC: P =0.049).There was no significant difference between the two groups in the decrease degree of the remaining serum indexes before and after treatment.The analysis of Sobs index and Shannon index of alpha diversity of intestinal microflora showed that compared with healthy control group,the alpha diversity of SOBS index and Shannon index in AP patients were significantly decreased(P < 0.05).Alpha diversity of lactulose group and rhubarb group decreased after treatment compared with before treatment,but the degree of decline was not statistically different between the two groups.The least square discriminant analysis(PLS-DA)of beta diversity showed that the biome distribution of AP patients and healthy control group could be clearly differentiated and showed a significant difference(P =0.001).There was no significant difference in the biome distribution between the lactilose group and the rhubarb group before treatment.After treatment,there was a significant difference in the biota distribution between the two groups in the subgroup without antibiotics(P =0.001),while there was no significant difference between the two groups in the subgroup with antibiotics.The analysis of intestinal microbial composition indicated that the abundance of Enterococcus、Escherichia-Shigella、Bacteroidetes,Streptococcus and other conditional pathogenic bacteria in AP patients was significantly higher than that in healthy control group.In the subgroups without antibiotics,the abundance of beneficial bacteria--Bifidobacterium in lactulose group increased significantly after treatment compared with before treatment,while the abundance of rhubarb group decreased.The abundance of conditional pathogenic bacteria such as Streptococcus and Veillonella increased after treatment in both groups,but the increase degree in rhubarb group was significantly higher than that in lactulose group.In the subgroups receiving antibiotics,the abundance of Bifidobacteria in the lactulose group was still significantly increased after treatment,while the abundance of Bifidobacteria in the rhubarb group was decreased.The beneficial bacteria-Lactobacillus showed an increasing trend in both groups.Enterococcus,Escherichia-Shigella and other harmful bacteria were increased after treatment in both groups,but the degree of increase in rhubarb was significantly higher than that in lactulose group.The main components of intestinal SCFAs were acetic acid,propionic acid and butyric acid,and the content of total SCFAs in AP patients was significantly lower than that in normal controls(P < 0.05).Total SCFAs and the contents of the three SCFAs in two groups were significantly increased after treatment compared with before treatment,and the degree of increase in the lactulose group was significantly higher than that in the rhubarb group(total SCFAs: P =0.005;Acetic acid: P =0.021;Propionic acid: P =0.043;Butyric acid: P =0.016).There was no significant difference in the remaining SCFAs between the two groups.Conclusion:Compared with the traditional Chinese medicine rhubarb,large dose of lactulose can not only improve the intestinal dysfunction and reduce systemic inflammation in MAP and MSAP patients,but also regulate intestinal flora and increase intestinal SCFAs content.Therefore,the application of lactulose in AP is worthy of promotion. |
