RESUMO
Objective To study the protective effect of pure carbachol or combined with dietary fiber on intestinal mucosal barrier of rats after diffuse brain injury (DBI).Methods An adult male Wistar rat model of DBI was reproduced by gravitational shock method. The rats injured and survived after resuscitation were divided into three groups: model group (n = 40), carbachol group (n = 40) and carbachol combined with dietary fiber group (combined group,n = 32). In addition, a control group was established by simply an incision performed on the scalp, and the rats could drink freely (n = 5). In the experimental groups, 2 hours after resuscitation the rats began to receive gavage, 6 hours once, the liquid amount 15 mL/kg should be assured in every 6 hours, and if insufficient, normal saline was supplemented. In model group, normal saline 90 mL/kg was given, in carbachol group, carbachol 300μg/kg was administered and in combined group, carbachol 300μg/kg combined with dietary fiber 60 mL/kg was supplied. At 3 (combined group being excluded), 6, 12, 24 and 48 hours after resuscitation, the rats were anesthetized to collect samples and detect the plasma levels of D-lactate and activity of diamine oxidase (DAO) respectively, and the changes of villus height of small intestine were examined by a light microscope.Results The plasma D-lactate levels and the activities of DAO at any time point in the experimental groups were significant higher than those in control group (allP < 0.01). Along with the prolongation of time, the levels of plasma D-lactate and DAO activities in carbachol and carbachol plus diatary fiber groups were gradually lower than those of the model group, and at 48 hours after injury they reached their valley values [D-lactate (ng/L): 6.32±0.79, 7.46±1.67 vs. 17.65±1.53, DAO activity (kU/L): 0.76±0.01, 0.86±0.01 vs. 2.23±0.15]. Under light microscopy, compared with control group, the villus height of small intestinal mucosa at any time point in any experimental group was gradually lowered, and reached the valley values at 12 hours, then gradually increased , and peaked at 48 hours, the villus height in carbachol group and combined group was higher than that in model group (μm: 265.36±10.20, 261.54±10.38 vs. 247.51±9.39, bothP < 0.05).Conclusion When only carbachol is administered into the rat intestine early after diffuse brain injury in rats, beginning from 6 hours after injury, the protective effect of intestinal mucosal barrier is shown, representing decrease of plasma D-lactate level and DAO activity, amelioration of intestinal mucosal damage and protection of intestinal mucosal barrier; under the same above situation, the carbachol combined with dietary fiber was applied, showing the similar above carbachol protective effects.
RESUMO
Objective To observe the protection of carbachol on intestinal barrier function in patients with trauma. Methods A prospective randomized controlled trial was conducted. Seventy patients after trauma with a definite diagnosis of multiple organ dysfunction syndrome(MODS)from Department of Critical Care Medicine in Hebei United University Affiliated Hospital were included. According to random number table,the patients were divided into a carbachol treatment group(37 cases)and a mosapride citrate treatment group(33 cases),and all the patients in the two groups were treated by antibacterial drugs,supportive agents for organ function,surgery, etc symptomatic treatment. Based on the conventional treatment,in the carbachol treatment group,carbachol was administered through a stomach tube at the dose of 0.2 mg/kg,twice a day,and the dose was doubled if no exhaust or defecation persisted for 3 days after treatment,while in the mosapride group,mosapride citrate was given at the dose of 5 mg once and thrice a day,the therapeutic course of both groups being 7 days. On the 1st,3rd,5th, 7th day after admission,peripheral venous fasting blood in early morning was collected,the activity of diamine oxidase(DAO),expression rates of CD11b+and CD18+in polymorphonuclear neutrophil(PMN),contents of tumour necrosis factor-α(TNF-α)and interleukin-10(IL-10) were detected,and the clinical curative effects were observed. Results Compared to the mosapride citrate treatment group,the total effective rate was significantly higher in the carbachol treatment group on the 7th day after treatment〔70.3%(26/37)vs. 45.5%(15/33),P<0.05〕. The activity of DAO,expression rates of CD11b+and CD18+in PMN,contents of TNF-αand IL-10 in the carbachol treatment group were decreased with the extension of time,and reached valley values on the 7th day,the differences were statistically significant in the comparisons with those in mosapride citrate treatment group at the same time point〔DAO(mg/L):3.21±0.52 vs. 3.93±0.51,CD11b+:(14.89±2.16)% vs.(28.92±1.59)%,CD18+:(53.67±2.44)% vs. (72.46±4.08)%, TNF-α(ng/L):111.44±16.42 vs. 129.73±18.74, IL-10(ng/L):67.71±38.83 vs. 121.45±40.23,all P<0.05〕. At the various time points,the above indexes had no obvious changes in mosapride citrate treatment group. Conclusion Carbachol can ameliorate the ischemic/reperfusion(I/R)injury in patients with intestinal barrier dysfunction after trauma,decrease the release of inflammatory cytokines in vivo,and promote peristalsis of intestinal tract,therefore carbachol has clinical value of protecting intestinal barrier function.