ABSTRACT
<p><b>OBJECTIVE</b>To investigate the changing laws of serum high mobility group box 1 protein (HMGB1) in septic rats and intervention effect of Xuebijing on it.</p><p><b>METHODS</b>Lipopolysaccharide (LPS) (5 mg/kg BW) was intravenously injected into the tail vein of healthy male Wistar rats to prepare the sepsis rat model. In Experiment 1: 50 Wistar rats were randomly divided into three groups, i.e., the normal group (A, n=10); the LPS model group (B, n=10), the LPS +Xuebijing treatment group (C, n=30). Rats in the C group were further divided into three subgroups, i.e., 2 h before LPS injection (group C1), 2 h after LPS injection (group C2), and 8 h after LPS injection (group C3), 10 in each group. Blood samples were collected from the caudal vein to detect serum HMGB1 levels by Western blot at 4, 12, 24, 48, and 72 h after LPS injection. Experiment 2: 30 Wistar rats were equally divided into the LPS model group (D) and the LPS + Xuebijing treatment group (E), 15 in each group. They were treated as rats in the B group and the C1 group respectively. Five rats were sacrificed at 12, 24, and 48 h after LPS injection in the two groups. Blood as well as the tissue samples were harvested to measure such indices as ALT, AST, Cr, and BUN, as well as pathological changes of liver, lung, and kidney.</p><p><b>RESULTS</b>(1) Compared with the A group, serum HMGB1 levels were higher at various time points in the B group (P < 0.05). Compared with the B group, serum HMGB1 levels at 12,24,48, and 72 h decreased in the C1, C2, and C3 groups. Besides, the decrease was more obvious at 24 h and 48 h.The decrement in the C3 group was less than that in the C1 and C2 groups (P < 0.05). (2) In the D group, ALT, AST, Cr, and BUN were significantly higher than those in the A group and reached the peak at 24 h (P < 0.05). Compared with the E group, AST, Cr, and BUN at 24 and 48 h, and ALT at each time point decreased significantly in the E group (P < 0.05). (3)The results of pathological section of liver, lung, and kidney showed local congestion and hemorrhage, cell edema/necrosis/degeneration, infiltration of inflammatory cells, damage of characteristic structures and so on; particularly serious lesion occurred at 24 and 48 h in the D group. The microscopic lesion was obviously alleviated in the E group than in the D group at corresponding time points.</p><p><b>CONCLUSIONS</b>The serum HMGB1 levels increased in septic rats, with late occurrence of peak value and longer duration of the high value. HMGB1 played an important role in excessive inflammatory response and multiple organ dysfunction. Xuebijing could reduce the serum levels of HMGB1, improve biochemical parameters, and attenuate severe inflammatory response of liver, lung, and kidney tissues in septic rats. Besides, the earlier use, the better effect obtained.</p>
Subject(s)
Animals , Male , Rats , Disease Models, Animal , Drugs, Chinese Herbal , Therapeutic Uses , HMGB1 Protein , Blood , Rats, Wistar , Sepsis , Blood , Drug TherapyABSTRACT
BACKGROUND: The gut is capable of inducing multiple organ dysfunction syndrome (MODS). In the diagnosis and treatment of critical ill patients, doctors should pay particular attention to the protection or recovery of intestinal barrier function. However, no reliable diagnostic criteria are available clinically. This study aimed to assess the changes of intestinal mucosal barrier function in surgically critical ill patients as well as their significance. METHODS: Thirty-eight surgically critical ill patients were enrolled as a study group (APACHE II>8 scores), and 15 non-critical ill patients without intestinal dysfunction were selected as a control group (APACHE II<6). General information, symptoms, physical signs, and APACHE II scores of the patients were recorded. The patients in the study group were subdivided into an intestinal dysfunction group (n=26) and a non-intestinal dysfunction group (n=12). Three ml venous blood was collected from the control group on admission and the same volume of plasma was collected from the study group both on admission and in the period of recovery. The plasma concentrations of endotoxin, diamine oxidase (DAO), D-lactate, and intestinal fatty-acid binding protein (iFABP) were detected respectively. The data collected were analyzed by the SPSS 17.0 software for Windows. RESULTS: The levels of variables were significantly higher in the study group than in the control group (P<0.01). They were higher in the intestinal dysfunction group than in the non-intestinal dysfunction group (DAO P<0.05, endotoxin, D-lactate, iFABP P<0.01). In the non-intestinal dysfunction group compared with the control group, the level of endotoxin was not significant (P>0.05), but the levels of DAO, D-lactate and iFABP were statistically significant (P<0.05). The levels of variables in acute stage were higher than those in recovery stage (P<0.01).The death group showed higher levels of variables than the survival group (endotoxin and D-lactate P<0.01, DAO and iFABP P<0.05). CONCLUSION: The plasma concentrations of endotoxin, DAO, D-lactate, and intestinal fatty-acid binding protein (iFABP) could reflect a better function of the intestinal mucosa barrier in surgically critical ill patients.