Dexmedetomidine attenuates acute kidney injury induced by hemorrhagic shock/resuscitation in rats / 中国病理生理杂志

AIM:To investigate the effects of dexmedetomidine on hemorrhagic shock /resuscitation(HS/R)-induced acute kidney injury(AKI)in rats,and to explore the possible mechanisms.METHODS:Wistar rats(n=32) were randomly divided into 4 groups(n =8): normal saline control group(NS group), dexmedetomidine group(D group),HS/R group and HS/R+D group.The animals were sacrificed at 6 h after resuscitation.The levels of serum creatinine(Cr)and blood urine nitrogen(BUN)were examined.The kidneys of all rats were removed for evaluation of histological characteristics,and the levels of malondialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin-1β (IL-1β)and superoxide dismutase(SOD)were measured.The expression of nuclear factor-κB(NF-κB)and hemeoxyge-nase-1(HO-1)was determined by Western blot.RESULTS: Compared with NS group, the levels of Cr, BUN, MDA, TNF-αand IL-1βwere obviously increased in HS/R group, which were obviously decreased in HS/R+D group(P<0.05).Compared with NS group,the SOD activity was obviously decreased in HS/R group,which was obviously increased in HS/R+D group(P<0.05).Compared with NS group, the protein expression of NF-κB was obviously increased in HS/R group,which was obviously decreased in HS/R+D group(P<0.05).Compared with NS group, the protein ex-pression of HO-1 was increased in HS/R group.Compared with HS/R group,the protein expression of HO-1 was obviously increased in HS/R+D group.Compared with NS group,HS/R induced marked kidney histological injury,which was less pronounced in HS/R+D group.CONCLUSION:Dexmedetomidine effectively protects rats against AKI caused by HS /R, and its mechanism may be associated with the increase in HO-1 expression and the inhibition of NF-κB expression.

Dexmedetomidine alleviates pulmonary edema by upregulating AQP1 and AQP5 expression in rats with acute lung injury induced by lipopolysaccharide / 华中科技大学学报（医学）（英德文版）

This study aims to elucidate the mechanisms by which dexmedetomidine alleviates pulmonary edema in rats with acute lung injury induced by lipopolysaccharide (LPS). Male Wistar rats were randomly divided into five groups: normal saline control (NS) group, receiving intravenous 0.9% normal saline (5 mL/kg); LPS group, receiving intravenous LPS (10 mg/kg); small-dose dexmedetomidine (S) group, treated with a small dose of dexmedetomidine (0.5 μg · kg(-1) · h(-1)); medium-dose dexmedetomidine (M) group, treated with a medium dose of dexmedetomidine (2.5 μg · kg(-1) · h(-1)); high-dose dexmedetomidine (H) group, treated with a high dose of dexmedetomidine (5 μg · kg(-1) · h(-1)). The rats were sacrificed 6 h after intravenous injection of LPS or NS, and the lungs were removed for evaluating histological characteristics and determining the lung wet/dry weight ratio (W/D). The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) in the lung tissues were assessed by enzyme- linked immunosorbent assay (ELISA). The mRNA and protein expression levels of aquaporin-1 (AQP1) and aquaporin-5 (AQP5) were detected by RT-PCR, immunohistochemistry, and Western blotting. The lung tissues from the LPS groups were significantly damaged, which were less pronounced in the H group but not in the small-dose dexmedetomidine group or medium-dose dexmedetomidine group. The W/D and the concentrations of TNF-α and IL-1β in the pulmonary tissues were increased in the LPS group as compared with those in NS group, which were reduced in the H group but not in S group or M group (P<0.01). The expression of AQP1 and AQP5 was lower in the LPS group than in the NS group, and significantly increased in the H group but not in the S group or M group (P<0.01). Our findings suggest that dexmedetomidine may alleviate pulmonary edema by increasing the expression of AQP-1 and AQP-5.

The influence of GABAA receptor on the analgesic action of intrathecally injected oxysophoridine / 药学学报

.This study is to investigate the analgesic effect produced by intrathecal injection (ith) of oxysophoridine (OSR) and the mechanism of GABAA receptor. Warm water tail-flick test was used to detect the analgesic effect of OSR (12.5, 6.25, and 3.13 mg.kg-1 ith) and to observe the influence of GABA (gamma aminobutyric acid) agonist or antagonist on the analgesic effect of OSR in mice. Immunohistochemistry method were used to detect the influence of OSR (12.5 mg.kg-1, ith) on the GABAARalpha1 protein expression in spinal cord. The results obtained covers that OSR (12.5 and 6.25 mg.kg-, ith) alleviates pain significantly with the warm water tail-flick test (P<0.05, P<0.01), the rate of pain threshold increases by 68.45%; GABA and muscimol (MUS) produces analgesic synergism together with the OSR, picrotoxin (PTX) and bicuculline (BIC) antagonize the analgesic effect of OSR; OSR (12.5 mg.kg-1, ith) significantly increase the positive number of GABAARalpha1 nerve cell in spinal cord (P<0.01) and significantly decrease the average grey levels (P<0.01). In conclusion, OSR intrathecal injection has significant analgesic effect. And GABAA receptor in spinal cord is involved in the analgesic mechanism.

Valproic acid attenuates the multiple-organ dysfunction in a rat model of septic shock / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Valproic acid (VPA) improves early survival and organ function in a highly lethal poly-trauma and hemorrhagic shock model or other severe insults. We assessed whether VPA could improve organ function in a rat model of septic shock and illustrated the possible mechanisms.</p><p><b>METHODS</b>Forty Sprague-Dawley rats were randomly assigned to four groups (n = 10): control group, VPA group, LPS group, and LPS + VPA group. Lipopolysaccharide (LPS) (10 mg/kg) was injected intravenously to replicate the experimental model of septic shock. Rats were treated with VPA (300 mg/kg, i.v.) or saline. Six hours after LPS injection, blood was sampled for gas analysis, measurement of serum alanine aminotransferase, aspartate aminotransferase, urine nitrogen, creatinine and tumor necrosis factor-alpha. Lung, liver and kidney were collected for histopathological assessment. In addition, myeloperoxidase activity and tumor necrosis factor-a in pulmonary tissue were measured. Acetylation of histone H3 in lung was also evaluated by Western blotting.</p><p><b>RESULTS</b>LPS resulted in a significant decrease in PaO2, which was increased by VPA administration followed LPS injection. In addition, LPS also induced an increase in the serum levels of alanine aminotransferase, aspartate aminotransferase, urine nitrogen, creatinine, and tumor necrosis factor-alpha. However, these increases were attenuated in the LPS + VPA group. The lungs, liver and kidneys from the LPS group were significantly damaged compared with the control group. However, the damage was attenuated in the LPS + VPA group. Myeloperoxidase activity and tumor necrosis factor-alpha levels in pulmonary tissue increased significantly in the LPS group compared with the control group. These increases were significantly inhibited in the LPS + VPA group. Acetylation of histone H3 in lung tissue in the LPS group was inhibited compared with the control. However, the level of acetylation of histone H3 in the LPS + VPA group was markedly elevated in contrast to the LPS group.</p><p><b>CONCLUSIONS</b>Treatment with VPA can attenuate multiple organ damage caused by LPS induced septic shock. Our data also suggest that the beneficial effects are in part due to the decrease in inflammatory cytokines and restoration of normal acetylation homeostasis.</p>

Reduction of pulmonary inflammatory response by erythropoietin in a rat model of endotoxaemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Erythropoietin elicits protective effects in lung tissue injury induced by ischaemic reperfusion and hyperoxia. We investigated the protective roles of erythropoietin in pulmonary inflammation and lung injury during acute endotoxaemia.</p><p><b>METHODS</b>A total of 32 male Sprague-Dawley rats were randomly assigned to four groups: saline group, erythropoietin + saline group, saline + lipopolysaccharide group and erythropoietin + lipopolysaccharide group. Rats were treated with erythropoietin (3000 U/kg, i.p.) or saline, 30 minutes prior to lipopolysaccharide administration (6 mg/kg, i.v.). Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Optical microscopy was performed to examine pathological changes in lungs. Wet/dry (W/D) ratios, myeloperoxidase activity, malondialdehyde concentrations and tumour necrosis factor-alpha (TNF-alpha) as well as interleukin 1 beta (IL-1beta) levels in lungs were measured. The pulmonary expression of nuclear factor kappaB (NF-kappaB) p65 was evaluated by Western blotting. Differences between the different groups were analysed by one-way analysis of variance (ANOVA).</p><p><b>RESULTS</b>The lung tissues from the saline + lipopolysaccharide group were significantly damaged, which were less pronounced in the erythropoietin + lipopolysaccharide group. The W/D ratio increased significantly in the saline + lipopolysaccharide group (5.75 +/- 0.22) as compared with the saline group (3.85 +/- 0.20) (P < 0.01), which was significantly reduced in the erythropoietin + lipopolysaccharide group (4.50 +/- 0.35) (P < 0.01). Myeloperoxidase activity and malondialdehyde levels increased significantly in the saline + lipopolysaccharide group compared with the saline group, which was reduced in the erythropoietin + lipopolysaccharide group. The TNF-alpha level of pulmonary tissue increased significantly in the saline + lipopolysaccharide group ((9.80 +/- 0.82) pg/mg protein) compared with the saline group ((4.20 +/- 0.42) pg/mg protein, P < 0.01). However, the increase of TNF-alpha level of pulmonary tissue was significantly reduced in the erythropoietin + lipopolysaccharide group ((6.50 +/- 0.66) pg/mg protein, P < 0.01). Similarly, pulmonary IL-1beta levels were elevated markedly in the saline + lipopolysaccharide group in contrast to the saline group, whereas the elevation was much less in the erythropoietin + lipopolysaccharide group. The nuclear localization of p65 increased markedly in the saline + lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the erythropoietin + lipopolysaccharide group.</p><p><b>CONCLUSION</b>Erythropoietin attenuates pulmonary inflammation and suppresses TNF-alpha and IL-1beta overproduction during acute endotoxaemia, which is partially mediated by inhibition of NF-kappaB.</p>

Melatonin reduces acute lung injury in endotoxemic rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Treatment with melatonin significantly reduces lung injury induced by bleomycin, paraquat and ischemia reperfusion. In the present study, we investigated the possible protective roles of melatonin in pulmonary inflammation and lung injury during acute endotoxemia.</p><p><b>METHODS</b>Thirty-two male Sprague-Dawley rats were randomly assigned to four groups: vehicle + saline group, melatonin + saline group, vehicle + lipopolysaccharide group, melatonin + lipopolysaccharide group. The rats were treated with melatonin (10 mg/kg, intraperitoneal injection (i.p.)) or vehicle (1% ethanol saline), 30 minutes prior to lipopolysaccharide administration (6 mg/kg, intravenous injection). Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Blood gas analysis was carried out. Optical microscopy was performed to examine pathological changes in lungs and lung injury score was assessed. Wet/dry ratios (W/D), myeloperoxidase activity, malondialdehyde concentrations and tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) levels in lungs were measured. The pulmonary expression of nuclear factor-kappa B (NF-kappaB) p65 was evaluated by Western blotting.</p><p><b>RESULTS</b>PaO(2) in the vehicle + lipopolysaccharide group decreased compared with that in the vehicle + saline group. This decrease was significantly reduced in the melatonin + lipopolysaccharide group. The lung tissues from the saline + lipopolysaccharide group were significantly damaged, which were less pronounced in the melatonin + lipopolysaccharide group. The W/D ratio increased significantly in the vehicle + lipopolysaccharide group (6.1 +/- 0.18) as compared with that in the vehicle + saline group (3.61 +/- 0.3) (P < 0.01), which was significantly reduced in the melatonin + lipopolysaccharide group (4.8 +/- 0.25) (P < 0.01). Myeloperoxidase activity and malondialdehyde levels increased significantly in the vehicle + lipopolysaccharide group compared with that in the vehicle + saline group, which was reduced in the melatonin + lipopolysaccharide group. The TNF-alpha level of pulmonary tissue increased significantly in the vehicle + lipopolysaccharide group ((8.7 +/- 0.91) pg/mg protein) compared with that in the vehicle + saline group ((4.3 +/- 0.62) pg/mg protein, P < 0.01). However, the increase of TNF-alpha level of pulmonary tissue was significantly reduced in the melatonin + lipopolysaccharide group ((5.9 +/- 0.56) pg/mg protein, P < 0.01). Pulmonary IL-10 levels were elevated markedly in the vehicle + lipopolysaccharide group in contrast to that in the vehicle + saline group, whereas the elevation was augmented in the melatonin + lipopolysaccharide group. The nuclear localization of p65 increased markedly in the vehicle + lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the melatonin + lipopolysaccharide group.</p><p><b>CONCLUSION</b>Melatonin reduces acute lung injury in endotoxemic rats by attenuating pulmonary inflammation and inhibiting NF-kappaB activation.</p>

Studies on analgesic effects and sites of oxymatrine-carbenoxolone sodium complex / 中国中药杂志

<p><b>OBJECTIVE</b>To study the analgesic effects and sites of oxymatrine-carbenoxolone sodium complex (OCSC).</p><p><b>METHOD</b>Adopting formalin test, warm water tail-flick test and intracerebroventricularly (icv) injection to observe the analgesic effects of OCSC in mice.</p><p><b>RESULT</b>Intraperitoneally injecting (ip) OCSC (75, 150 mg x kg(-1)) remarkedly inhibited the pain of mice in the formalin test and prolonged latent phases of tail-shrinking of mice, icy OCSC (1.875, 3.75, 7.5 mg x kg(-1)) significantly prolonged latent phases of tail-shrinking of mice, it had dose-dependent effect with concentration.</p><p><b>CONCLUSION</b>The result indicated that OCSC has obvious analgesic effects and its mechanism may be involved in central nervous system (CNS).</p>

Effect of bismuth glycyrrhizate on experimental gastric ulcers and its mechanisms / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the ulcer-preventive effect of bismuth glycyrrhizate on experimental gastric ulcer and its mechanisms.</p><p><b>METHOD</b>Three kinds of model animals with experimental gastric ulcer were established and gastric mucosal injuries were induced by pyloric ligation in rats, applying ethanol in rats and imposing stress in mice, respectively. The rats were divided into experimental groups treated with bismuth glycyrrhizat 700, 350, 175 mg kg(-1), positive control group treated with cimetidine (200 mg kg(-1), and negative control group treated with 0.1% EDTA. The mice were divided into experimental groups treated with bismuth glycyrrhiza 980, 490, 250 mg kg(-1). The gastric ulcer index, gastric juice volume, acidity, pepsin activity, the level of nitric oxide (NO) in serum and the level of prostaglandin E2 in gastric tissue were measured in rats.</p><p><b>RESULT</b>Bismuth glycyrrhizate was shown to be able to reduce the gastric juice volume, acidity and pepsin activity as well as gastric ulcer index. It could increase the content of NO in serum and the content of prostaglandin E2 in gastric tissue.</p><p><b>CONCLUSION</b>The bismuth glycyrrhizate has antiulcer effect in rats.</p>

Effects of oxysophoridine on Glu and GABA immuno-reaction positive neurons in cortex and hippocampus of rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of oxysophoridine (OSR) on glutamate (Glu) and gamma aminobutyric acid (GABA) immuno-reaction positive neurons in the cortex and hippocampus of rats.</p><p><b>METHOD</b>Immunohistochemistry method (SABC) and the micrographic analysis technique were employed to monitor the effect of OSR in the variations of Glu and GABA immunoreaction positive neurons in the cortex and hippocampus of rats.</p><p><b>RESULT</b>OSR administrated icv (10 mg) significantly increased the number of GABA immuno-reaction positive neurons while decreasing the number of glu immunoreaction positive neurons in cortex and hippocampus in rats (P < 0.05).</p><p><b>CONCLUSION</b>Results showed that the change of Glu and GABA caused by OSR may responsible for its inhibitory effects on the central nervous system.</p>

Analgesic effect of oxysophoridine and its mechanism / 中草药

Objective To investigate the analgesic effect of oxysophoridine(OSR)and the influence of verapamil(Ver)on the antinociception of OSR when two drugs were co-administrated in mice.Methods The number of writhing within 15 min after ip different doses of OSR was observed in painful mouse mo- dels caused by acetic acid.The hot plate method was used to assess nociceptive sensitivity of CaCl_2 and Ver before ip OSR.Nitric oxide(NO)in serum was measured by spectrophotometry.Results The number of writhing was decreased and the latency of licking the hind paws was prolonged in a dose-dependent manner after ip OSR.The antinociception of OSR could be antagonized by CaCl_2 and enhanced by Ver.No inter- ference was detected in serum volume of NO.Conclusion These results suggest that OSR can antagonize the acute pain caused by acetic acid and hot plate in a dose-dependent manner in mice.Calcium channel blocker could enhance the effect of OSR.