Objective To observe the effects of dexmedetomidine (DEX) on the expressions of TNF-α, IL-1β and apoptosis-related proteins in rat mesenteric artery.Methods Male SD rats of SPF grade were sacrificed and the mesenteric artery was separated under the stereo-microscope.We established an experimental model of vascular injury induced by lipopolysaccharide (LPS) and randomly divided the injured vessels into dexmedetomidine treatment group and control group.DEX treatment group was divided into 10-8, 10-7, and 10-6 mol/L subgroups according to the different concentrations of DEX.RNA and total protein was extracted in each group.The mRNA expressions of TNF-α, IL-1β and CaSR were detected by RT-PCR and the protein expression of TNF-α, Caspase-3 and AMPK were tested by Western blot.Results DEX (10-8, 10-7, and 10-6mol/L) obviously reduced vascular inflammatory reaction induced by lipopolysaccharide, reduced the mRNA and protein expressions of TNF-α as well as mRNA expression of IL-1β.Caspase 3 protein expression significantly lowered in blood vessels in DEX group compared with LPS group.DEX had no obvious effect on lipopolysaccharide-induced vascular AMPK and CaSR mRNA or protein expressions.Conclusion DEX obviously deceased the expressions of inflammation-related proteins, suggesting that DEX has anti-inflammatory effects.

Objective To investigate the dilating effect of dexmedetomidine (DEX)on isolated vascular smooth muscles and to explore the mechanism.Methods Tension of isolated mesenteric arterial rings of male Sprague-Dawley rats was recorded.The effects of DEX on the rings and the effects of DEX on vascular reaction induced by various drugs were recorded. Results DEX completely relaxed the contraction induced by phenylephrine (PE)and KCl in a concentration-dependent manner in endothelium intact mesenteric arterial rings in rats.The vasodilating effect of DEX was increased by sodium nitroprusside.In phenylephrine (10-5 mol/L)based on pre-vasoconstriction,adding acetylcholine could not suppress DEX’s vasodilating effect.Vasodilation was not related to the endothelial cells.In physiological saline solution without calcium,DEX significantly inhibited the contraction induced by addition of CaCl2 .Conclusion DEX can induce vasodilation in a concentration-dependent manner,which is not dependent on the endothelial cells.

Objective To evaluate the effect of recombinant human erythropoietin (rHuEPO) on lung injury induced by hepatic ischemia-reperfusion (I/R) in rats.Methods Sixty healthy male SpragueDawley rats, aged 6-8 weeks, weighing 220-280 g, were randomly divided into 3 groups (n=20 each) using a random number table: sham operation group (group S) , hepatic I/R group (group I/R), and rHuEPO group (group E).I/R and E groups underwent I/R of 70 percent of the liver.The rHuEPO 4 000 U/kg was injected intraperitoneally at 24 h before I/R in group E, while the equal volume of normal saline was given in S and I/R groups.The rats were sacrificed at 3 h of reperfusion, and lungs were removed and cut into sections which were stained with haematoxylin and eosin and examined under light microscope.Wet to dry lung weight ratio (W/D ratio) was calculated.The expression of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) in lung tissues was determined by immunohistochemistry.The content of malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and myeloperoxidase (MPO) in lung tissues were detected.Results Compared with group S, the W/D ratio, MDA content, and MPO activity were significantly increased, the SOD activity was decreased, the expression of HO-1 and iNOS was up-regulated (P＜0.05) , and the pathological changes of lung tissues were obvious in E and I/R groups.Compared with group I/R, the W/D ratio, MDA content, and MPO activity were significantly decreased, the SOD activity was increased, the expression of HO-1 was up-regulated, the expression of iNOS was down-regulated (P＜0.05) , and the pathological changes of lung tissues were reduced in group E.Conclusion The rHuEPO can alleviate hepatic I/R-induced lung injury in rats, and the mechanism may be related to up-regulated expression of HO-1 and down-regulated expression of iNOS.

【Objective】 To investigate the effects of dexmedetomidine (DEX) intervention on the expressions of chondrocytes and related factors in vitro and its possible molecular mechanisms. 【Methods】 C28/I2 normal human chondrocyte lines were cultured in vitro, and dexmedetomidine at the concentration of 1 μmol/L was selected to intervene for 24 h and 48 h, respectively. The morphology and cell density of chondrocytes were observed after DEX culture at different time points. Immunofluorescence technique was used to detect the expression levels of disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) in chondrocytes in each group. The expression levels of Adamts5, aggrecan (Acan), versican (Vcan), Furin, proprotein convertase subtilisin/kexin type 6 (Pcsk6), collagen type Ⅰ alpha 1 (Col1a1), collagen type Ⅱ alpha 1 (Col2a1), collagen type X alpha 1 (Col10a1), and SRY2 related high mobility group box gene9 (Sox9) were detected by RT-PCR. Adamts5 gene knockout chondrocytes were constructed by lentivirus transfection technology and treated with DEX; RT-PCR was used to detect the effects of DEX on the expression levels of Acan, Vcan, Furin, Pcsk6 and Sox9 after Adamts5 gene knockout. 【Results】 After 24 and 48 h of intervention with 1 μmol/L DEX, the morphology and size of chondrocytes did not change significantly, but the cell density increased slightly. Immunofluorescence assay showed that the expression of ADAMTS5 increased at first and then decreased after DEX treatment for 24 and 48h, respectively (P=0.032). RT-PCR results showed that with the extension of intervention time, the expression of Adamts5 first increased and then decreased. The expression difference between 48 and 24 h after culture was statistically significant (P=0.032). The change trend of Pcsk6 was the same as that of Adamts5, while the change trend of Acan expression was opposite that of Adamts5. Chondrocytes knocked out Adamts5 gene and intervened with DEX for 24 and 48 h. The results of RT-PCR showed that the expression of Pcsk6 decreased while that of Acan increased and the changes were significant. 【Conclusion】 Dexmedetomidine may activate ADAMTS5 zymogen through Pcsk6, thereby promoting proteoglycan degradation in chondrocytes.