Protective effects of Ligustrazine, Kakonein and Panax Notoginsenoside on the small intestine and immune organs of rats with severe acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (SAP) is characterized by fatal pathogenic conditions and a high mortality. It is important to study SAP complicated with multiple organ injury. In this study we compared the protective effects of three traditional Chinese medicines (Ligustrazine, Kakonein and Panax Notoginsenoside) on the small intestine and immune organs (thymus, spleen and lymph nodes) of rats with SAP and explored their mechanism of action. METHODS: One hundred forty-four rats with SAP were randomly divided into model control, Ligustrazine-treated, Kakonein-treated, and Panax Notoginsenoside-treated groups (n=36 per group). Another 36 normal rats comprised the sham-operated group. According to the different time points after operation, the experimental rats in each group were subdivided into 3-, 6- and 12-hour subgroups (n=12). At various time points after operation, the mortality rate of rats and pathological changes in the small intestine and immune organs were recorded and the serum amylase levels were measured. RESULTS: Compared to the model control groups, the mortality rates in all treated groups declined and the pathological changes in the small intestine and immune tissues were relieved to different degrees. The serum amylase levels in the three treated groups were significantly lower than those in the model control group at 12 hours. The pathological severity scores for the small intestinal mucosa, thymus and spleen (at 3 and 12 hours) in the Ligustrazine-treated group, for the thymus (at 3 and 12 hours) and spleen (at 3 and 6 hours) in the Kakonein-treated group, and for the thymus (at 3 hours) and spleen (at 3 hours) in the Panax Notoginsenoside-treated group were significantly lower than those in the model control group. The pathological severity scores of the small intestinal mucosa (at 6 and 12 hours) and thymus (at 6 hours) in the Ligustrazine-treated group were significantly lower than those in the Kakonein- and Panax Notoginsenoside-treated groups. CONCLUSIONS: All the three traditional Chinese drugs significantly alleviated the pathological changes in the small intestine and immune organs of SAP rats. Ligustrazine was the most effective one among them.

Effect of Danshen on apoptosis and NF-κB protein expression of the intestinal mucosa of rats with severe acute pancreatitis or obstructive jaundice.

BACKGROUND: Intestinal mucosa injury in cases of severe acute pancreatitis (SAP) or obstructive jaundice (OJ) is one of the main reasons for the accelerated aggravation of these diseases. Besides being an organ to digest and absorb nutrients, the intestine is also a unique immune organ. When SAP and OJ develop, the destruction of the intestinal mucosa barrier is an important contributing factor for the development of bacterial translocation, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. It is important to protect the intestinal mucosa in the therapy for SAP and OJ. In this study, we determined the effect of Radix Salviae Miltiorrhizae (Danshen) injection on apoptosis and NF-κB P65 protein expression in the intestinal mucosa of rats with SAP or OJ, and explored the protective mechanism of Danshen in their mucosa. METHODS: Sprague-Dawley rats were used in the SAP and OJ experiments. These rats were randomly divided into sham-operated, model control, and treated groups. At various times after operation, the mortality rates were calculated. Subsequently, the rats were killed to assess the pathological changes, the expression levels of Bax and NF-κB proteins, and the apoptosis indices in the intestinal mucosa. RESULTS: Compared to the corresponding model control group, the number of SAP or OJ rats that died in the treated group decreased but showed no statistically significant difference. At all time points after operation, there was no significant difference between the treated and model control groups in the staining intensity as well as the product of staining intensity and positive staining rate of Bax protein in the intestinal mucosa of SAP and OJ rats . At 3 hours after operation, the apoptosis index of the intestinal mucosa of SAP rats in the treated group was lower than that in the model control group (P<0.01). At 12 hours after operation in SAP rats and 28 days after operation in OJ rats, the staining intensity as well as the product of staining intensity and positive staining rate of NF-κB protein of the intestinal mucosa in the treated group were lower than those in the model control group (P<0.01). CONCLUSION: Danshen exerts protective effects on the intestinal mucosa of SAP and OJ rats perhaps by inhibiting apoptosis and down-regulating NF-κB protein.

Protective effect of Radix Astragali injection on immune organs of rats with obstructive jaundice and its mechanism.

AIM: To observe the protective effect of Radix Astragali injection on immune organs (lymph nodes, spleen and thymus) of rats with obstructive jaundice (OJ) and its mechanism. METHODS: SD rats were randomly divided into sham-operation group, model control group and Radix Astragali treatment group. On days 7, 14, 21 and 28 after operation, mortality rate of rats, pathological changes in immune organs, expression levels of Bax and nuclear factor (NF)-kappaB p65 proteins, apoptosis indexes and serum tumor necrosis factor (TNF)-alpha level in spleen and thymus were observed, respectively. RESULTS: Compared to model control group, the number of dead OJ rats in Radix Astragali treatment group decreased (P > 0.05). The TNF-alpha level (27.62 +/- 12.61 vs 29.55 +/- 18.02, 24.61 +/- 9.09 vs 31.52 +/- 10.95) on days 7 and 21, the pathological severity score for spleen [0.0 (0.0) vs 0.0 (2.0) on days 7 and 14 and for lymph nodes [0.0 (1.0) vs 1.0 (2.0), 1.0 (0.0) vs 2.0 (1.0)] on days 21 and 28, the product staining intensity and positive rate of Bax protein in spleen [0.0 (0.0) vs 1.0 (2.0), 0.0 (1.0) vs 2.0 (1.5) and thymus [0.0 (0.0) vs 1.0 (2.0), 0.0 (1.0) vs 2.0 (1.5)] on days 14 and 28, the apoptotic indexes [0.0 (0.0) vs 0.0 (0.01)] in spleen and thymus [0.0 (0.0) vs 0.0 (0.01) on days 14 and 21 were significantly lower in Radix Astragali treatment group than in model control group (P < 0.05). CONCLUSION: Radix Astragali has protective effects on immune organs of OJ rats by relieving the pathological changes in immune organs, reducing TNF-alpha level and inhibiting Bax expression and apoptosis in spleen and thymus.

Tissue microarrays in pathological examination of apoptotic acinar cells induced by dexamethasone in the pancreas of rats with severe acute pancreatitis.

BACKGROUND: The good therapeutic effects of large dose of dexamethasone on severe acute pancreatitis (SAP) patients have been proved. This study was designed to investigate the influence of dexamethasone on apoptosis of acinar cells in the pancreas of rats with SAP and the protein expression of the apoptosis-regulating genes Bax and Bcl-2. METHODS: Ninety Sprague-Dawley rats with SAP were randomly divided into a model group and a dexamethasone treated group (45 rats in each group), and another 45 rats formed the sham operation group. Survival rates were calculated and gross pathological changes in the pancreas of each group were observed under a light microscope 3, 6 and 12 hours after operation. Tissue microarray technology was applied to prepare pancreatic tissue sections. The changes in Bax and Bcl-2 protein expression levels of pancreatic tissues from each group were assessed by immunohistochemical staining, and TUNEL staining was used to evaluate changes in apoptosis index. RESULTS: The model and treated groups did not differ in mortality at each time point. The pathological score for the pancreas in the treated group was significantly lower than that in the model group at 3 and 6 hours. The positive rates of Bax protein expression in the head and tail of the pancreas in the treated group at all time points were all markedly higher than those of the model group. The positive rate of Bcl-2 protein expression in the head of the pancreas in the treated group was significantly higher than that of the model group at 3 hours. TUNEL staining showed that the pancreas head and tail apoptosis indices of the treated group were markedly higher than those of the model group after 6 hours. CONCLUSIONS: Apoptosis may be a protective response to pancreatic cell injury. The mechanism of action of dexamethasone in treating SAP may be related to the apoptosis of acinar cells in the pancreas induced by apoptosis-regulating genes such as Bax and Bcl-2. The advantages of tissue microarrays in pathological examination of the pancreas include saving of time and energy, efficiency and highly representative.

Study of the protective effects of dexamethasone on multiple organ injury in rats with severe acute pancreatitis.

CONTEXT: Pancreas, lung, kidney and liver injury has been proven to play an important role in severe acute pancreatitis. OBJECTIVE: To observe the protective effects of dexamethasone on multiple organs (pancreas, lung, kidney and liver) in rats with severe acute pancreatitis. ANIMALS: One hundred and thirty-five Sprague-Dawley rats. DESIGN: Ninety rats were prepared as severe acute pancreatitis models and were randomly divided into a control group and the dexamethasone treatment group (45 rats in each group). Another 45 rats were selected to be the sham operation group. Each group was randomly subdivided into 3 subgroups which were observed at 3, 6, and 12 h after surgery (15 rats in each subgroup). MAIN OUTCOME MEASURES: The survival, gross and pathological findings under the light microscope, and the pathological scores of multiple organs in each group were recorded. RESULTS: There was no significant difference in survival between the dexamethasone treatment group and the control group (P=0.494). The pancreas pathological score was significantly lower in the dexamethasone treatment group than in the control group at the various time intervals (overall: P<0.001; 3 h: P=0.019; 6 h: P=0.010, 12 h: P<0.001). The lung pathological score was significantly lower in the dexamethasone treatment group than in the control group at 6 and 12 h (P=0.023 and P<0.001, respectively). The kidney (P<0.001) and liver (P=0.009) pathological scores were also significantly lower in the overall dexamethasone treatment group than in the overall control group, but significant differences were found only in some time intervals (kidney: 6 and 12 h, P=0.006 and P=0.044, respectively; liver: 12 h, P=0.046). CONCLUSION: Intravenous injection of dexamethasone can alleviate pancreas, lung, kidney and liver injury of rats with severe acute pancreatitis and may have protective effects on multiple organ injury.