Xuebijing Injection () increases early survival rate by alleviating pulmonary vasopermeability in rats subjected to severe burns.

OBJECTIVE: To investigate the effects of Xuebijing Injection (, XBJ) on survival rate and pulmonary vasopermeability in a rat model of severe scald injury. METHODS: Rats were divided into two experiments: experiment 1 was monitored for 12 h post-injury for survival analysis after severe burns; in experiment 2, rats were killed for determination of pulmonary vascular permeability and pro-inflflammatory mediators. In both experiments, rats were subject to third-degree 50% total body surface area (TBSA) burns or sham injury followed by XBJ or normal saline (NS) treatment. In addition, rat pulmonary microvascular endothelium cells (PMECs) were pretreated with either XBJ or phosphate buffer saline (PBS), and then subjected to sham serum or scald serum stimulation for 2 or 6 h, followed by transwell examination for the permeability of PMECs. Meanwhile, pro-inflflammatory mediators in PMECs culture supernatant were also investigated. RESULTS: The average survival time in the scald+XBJ group was 582.1±21.2 min, which was signifificantly longer than that in the scald + NS group (345.8±25.4 min, P<0.01). Plasma levels of tumor necrosis factor-alpha (TNF-α), E-selectin, interleukin-6 (IL-6), vascular permeability and water content of lung tissues were signifificantly increased in animals after severe burns (P<0.01). However, administration of XBJ signifificantly decreased these levels in plasma and lung tissue. In in vitro cell experiments, XBJ markedly attenuated permeability in PMECs monolayer and reduced the levels of TNF-α, IL-6 and soluble E-selectin after stimulation with scald serum (P<0.01). CONCLUSIONS: XBJ increases early survival rate by alleviating pulmonary vasopermeability and inhibiting pro-inflflammatory mediators in rats subjected to lethal scald injury. XBJ may be a potent drug in treatment of severe burns.

Valproic acid treatment attenuates caspase-3 activation and improves survival after lethal burn injury in a rodent model.

Burn injury may result in multiple organ dysfunction partially because of apoptotic cell death. The authors have previously shown that valproic acid (VPA) improves survival in a dog burn model. The aim of this study is to examine whether a VPA improves survival in a rodent burn model and whether this was because of inhibition of cell apoptosis. Rats were subjected to third-degree 55% TBSA burns and randomized to treatment with a VPA (300 mg/kg) or normal saline. One group of animals was monitored for 12 hours for survival analysis; another group was killed at 6 hours after injury, and brains, hearts, and blood samples were harvested for examination. Plasma creatine kinase (CK)-MB activities and neuron-specific enolase (NSE) levels were measured to evaluate the cardiac and brain damages. The effects of a VPA on acetylation of histone H3 and caspase-3 activation were also evaluated. Major burn injury resulted in a significant decrease in the acetylation of histone H3, and there was an increase in plasma CK-MB activities, NSE concentrations, and tissue levels of activated caspase-3. A VPA treatment significantly increased the acetylation of histone H3 and survival of the animals after major burn injury. In addition, a VPA treatment significantly attenuated the plasma CK-MB activities, an NSE concentrations, and inhibited caspase-3 activation after major burn injury. These results indicate that a VPA can attenuate cardiac and brain injury, and can improve survival in a rodent model of lethal burn injury. These protective effects may be mediated in part through the inhibition of caspase-3 activation.

The effects of ulinastatin on systemic inflammation, visceral vasopermeability and tissue water content in rats with scald injury.

BACKGROUND: The aim of this study was to examine whether administration of ulinastatin inhibits pro-inflammatory mediators and ameliorate visceral vasopermeability both in a rat model of major burn, and also in rat cultured endothelial cells stimulated with permeability-evoking mediators. METHODS: Plasma levels of tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), myeloperoxidase (MPO), microvascular permeability, and water content of organ tissues were evaluated in a rodent model of a 55% TBSA full-thickness scald injury. Microvascular permeability was also evaluated with a cultured pulmonary microvascular endothelial cells (PMECs) monolayer after stimulation with trypsin, bradykinin, histamine, prostaglandin E2 and burn serum. RESULTS: We found that the plasma levels of TNF-α, CRP, MPO, vascular permeability and water content of heart, lung, kidney, and small intestine tissues were significantly increased in animals after scald injury, and administration of ulinastatin lowered the levels TNF-α, CRP, MPO, vascular permeability and water content of those organ tissues. In vitro, ulinastatin lowered the levels of TNF-α, interleukin-6 (IL-6) and attenuated permeability in PMEC monolayers after being stimulated with burn serum or trypsin, but not by bradykinin, histamine or prostaglandin E2. CONCLUSIONS: These results indicate that ulinastatin attenuates the systemic inflammatory response and visceral vasopermeability both in vivo and vitro, and may serve as a therapeutic agent for prevention of systemic inflammatory response and leakage of fluid into tissue after major burn.

[Effects of electroacupuncture on hepatic blood flow and lipid peroxidation in septic rats].

OBJECTIVE: To investigate the protection effects of electroacupuncture on injury of lipid peroxidation induced by liver ischemia in septic rats. METHODS: Forty-eight male SD rats were subjected to sepsis induced by cecal ligation and puncture (CLP), and were randomly divided into a Sham operation group (group A), a CLP model group (group B), a CLP model plus electroacupuncture at "Zusanli" (ST 36) group (group C), a CLP model plus electroacupuncture at the shame acupoint (group D), a vagotomy plus CLP model group (group E) and CLP model plus electroacupuncture group after vagotomy (group F), 8 rats in each group. CLP was performed in group E and group F after the abdominal vagotomy. Bilateral "Zusanli"(ST 36) points and the shame acupoint were electroacupunctured (2 mA, 2/100 Hz) for 1 hour in group C, group F and group D, respectively. The hepatic blood flow (HBF) was detected by a laser-Doppler flowmetry at 6 h after CLP. The plasma activity of alanine aminotransferase (ALT) was also determined and specimens of liver were harvested for evaluation of malondialdehyde (MDA), xanthine oxidase (XOD) and assessment of the rate of water content. RESULTS: The blood flow of the liver was (56.97 +/- 11.95) U in group C which was significantly lower than (80.12 +/- 19.57) U in group A but higher than (42.61 +/- 10.97) U in group B, (44.53 +/- 9.23) U in group D, (30.05 +/- 4.46) U in group E and (30.46 +/- 6.38) U in group F (all P < 0.05) 6 h after CLP. Meanwhile, the levels of MDA, XOD, ALT and the rates of water content in liver in group C were all significantly higher than those in group A, but lower than those in the other four groups (all P < 0.05). The levels of MDA, XOD, ALT and the rates of water content in liver in group E and group F were all significantly higher than those in group D (all P < 0.05), while the blood flow of the liver lower than that in group D (P < 0.05), and with no significant differences in all above measurements between group E and group F (all P > 0. 05). CONCLUSION: Electroacupuncture at "Zusanli" (ST 36) can promote hepatic blood flow, inhibit lipid peroxidation and alleviate hepatic edema and dysfunction in septic rats, which might be related with the completeness of cranial nerve.

[The protective effects of carbachol on visceral ischemia-induced lipid peroxidation injury in rats with sepsis].

OBJECTIVE: To investigate the effect of carbachol (CAR) on visceral perfusion and lipid oxidation injury in rats with sepsis. METHODS: Sixty-four Sprague-Dawley (SD) rats received cecal ligation and puncture (CLP) surgery, and they were divided randomly into two groups: septic model group (CLP group, n=32) and septic model with CAR-treatment group (CAR group, n=32). CAR (10 microg/kg, CAR group) or normal saline (CLP group) was immediately injected into penial vein. Sixteen animals in each group were used to observe the mortality rates 12 hours and 24 hours after CLP, and the remaining rats for measurement of variables of blood and tissue. At the 18 hours after CLP, the mean arterial pressure (MAP), the blood flow (BF) of liver, kidney and jejunum, the plasma levels of alanine aminotransferase (ALT) and creatinine (Cr) were measured. Animals were sacrificed after the aforementioned determinations, and specimens of liver, kidney and jejunum were harvested for evaluation of malondialdehyde (MDA), xanthine oxidase (XOD), and assessment of tissue water content (ratio of dry to wet weight) of those organs . The activity of diamine oxidase (DAO) in jejunal tissue was detected. RESULTS: The mortality rates of 12 hours and 24 hours of CAR group were 25.0% (4/16)and 50.0% (8/16) respectively, all significantly lower than those of CLP group [37.5% (6/16) and 75%(12/16), both P<0.05]. CAR treatment did not result in significant statistical difference in the levels of MAP compared with CLP group at 18 hours after CLP (P>0.05), but led to significant increases in BF of CAR group in liver, kidney and jejunum compared with those of CLP group (all P<0.05). The levels of XOD and MDA, as well as the tissue water content were significantly lower in CAR group than CLP group in kidney and jejunum (all P<0.05). The parameters of organ function were significantly different in CAR group compared with CLP group [ALT: (64.3+/- 8.3) U/L vs. (81.5+/-7.9) U/L, Cr: (96.4+/-7.0) micromol/L vs. (117.1+/-6.7) micromol/L, DAO: (0.20+/- 0.04) U/L vs. (0.12+/-0.03) U/L, all P<0.05]. CONCLUSION: The results indicate that CAR promotes visceral perfusion, inhibits lipid peroxidation production and alleviates visceral edema and dysfunction in rats with sepsis.

[The effects of electro-acupuncturing at Zusanli point on intestinal proinflammatory factors, diamine oxidase and tissue water content in rats with sepsis].

OBJECTIVE: To investigate the protective effect of electro-acupuncturing (EA) at Zusanli point on sepsis induced ischemic and oxygen free radical intestinal injury in rats with sepsis. METHODS: Thirty-two male Wistar rats were used to reproduce sepsis by cecal ligation and puncture (CLP), and they were randomly divided into four groups (each n=8): CLP+EA (CLP/EA), CLP+sham EA (CLP/SEA), vagotomy+CLP+SEA (VA/CLP/SEA) and vagotomy+CLP+EA (VA/CLP/EA). Zusanli point was electro-acupunctured with constant voltage (2-100 Hz,2 mA for 30 minutes) immediately after CLP surgery. Abdominal vagotomy was performed in rats in VA/CL/SEA and VA/CLP/SEA groups. Six hours after CLP, the mucosal blood flow of jejunum (JMBF) was measured. Animals were sacrificed after 6 hours and specimens of jejunum were harvested for evaluation of malondialdehyde (MDA), xanthine oxidase (XOD), diamine oxidase (DAO) and assessment of the water content (WCR). RESULTS: JMBF and the activity of DAO of CLP/EA group were markedly higher, and the levels of XOD, MDA and WCR in jejunal tissue were obviously lower than those of CLP/SEA group (all P<0.05). The levels of JMBF and DAO of the VA/CLP/SEA group and VA/CLP/EA group were significantly lower, and XOD, MDA and WCR obviously higher than those of the CLP/EA group ( all P<0.05 ). There were no statistically differences in all above measurements between the VA/CLP/EA group and the VA/CLP/SEA group (all P>0.05). CONCLUSION: The results indicate that EA at Zusanli point obviously increased JMBF and DAO, and alleviated tissue edema and insult of intestinal mucosa. Vagotomy could weaken or eliminate the effects of EA. It is suggested that cholinergic anti-inflammatory pathway is one of the main mechanisms of intestinal protective effect of EA at Zusanli point.