Anti-inflammatory Effects And Mechanisms Of Dexmedetomidine Intraperitoneal Injection On Acute Peritonitis In Mice

Exp1Objective To explore the anti-inflammatory effects of different doses of dexmedetomidine intraperitoneal injection on acute peritonitis mice.Methods 84 healthy male mice were divided into 7 groups(n=12)by random number table method: control group(NS group),acute peritonitis group(AP group),and 5 different doses of dexmedetomidine group(Dex1-5 group).Acute peritonitis model was prepared by intraperitoneal injection of 0.1 mL of 2% acetic acid in mice of the AP group and Dex1-5 group,and an equal amount of saline was injected intraperitoneally in NS group.Mice in the Dex1-5 group was intraperitoneally injected with dexmedetomidine 20,50,100,200,400 ?g / kg(0.1 mL / 10 g)at 15 min after modeling.Mice in the NS group and AP group were intraperitoneally injected with the same volume of normal saline.The sedation scores of mice were mesured at 15 min after dosing,The heart rate of the mice was monitored at 30 minutes.At 24 h,use a fully automatic blood analyzer to measure the serum white blood cell count of mice and ELISA method to detect the concentration of TNF-? and IL-10 in peritoneal tissue.Histopathological changes of peritoneum were observed under light microscope.Results Compared with the NS group,the white blood cell count,TNF-?concentration,and IL-10 concentration in the AP group,Dex1 group,and Dex2 group were significantly increased(P(27)0.05).Compared with the AP group,the white blood cell count,TNF-? concentration,and IL-10 concentration in the Dex 3-5 group were significantly reduced(P(27)0.05),and the TNF-? concentration in the Dex2 group was significantly reduced(P(27)0.05).Compared with the Dex1 group,the white blood cell count,TNF-? concentration and IL-10 concentration in the peritoneal tissue in theDex3-5 group were significantly reduced(P(27)0.05).Only TNF-? concentration in mice in Dex2 group was significantly reduced(P(27)0.05).Compared with Dex2 group,the concentrations of TNF-? and IL-10 in peritoneal tissue of mice in Dex3-5 group were significantly reduced(P(27)0.05).Under 100 x light microscope,compared with the AP group,the peritoneal histopathological damage in the Dex1-5 group was reduced,and the pathological changes in the Dex3-5 group were closest to those in the NS group.Conclusion Intraperitoneal injection of dexmedetomidine can inhibit the inflammatory response of acute peritonitis in mice,and produce the best anti-inflammatory effect when the dose reaches 100 ?g/kg,and the anti-inflammatory effect does not increase with the increase of the dose.Exp2Objective To study the mechanism of intraperitoneal injection of dexmedetomidine in inhibiting acute peritonitis inflammation in mice.Methods 48 healthy male mice were divided into 4 groups(n=12)by random number table method: control group(NS group),acute peritonitis group(AP group),dexmedetomidine group(Dex group)and dexmedetomidine + wortmannin group(Dex + Wort group).AP group,Dex group and Dex + Wort group mice were intraperitoneally injected with 2% acetic acid 0.1 mL to prepare acute peritonitis model.NS group mice was intraperitoneally injected with the same amount of normal saline.Four hours prior to modeling,Dex + Wort group mice was injected intraperitoneally with 1.14 mg / kg(0.1 ml / 10 g)of wortmannin.At 15 min after modeling,Dex group and Dex + Wort group mice were intraperitoneally injected with dexmedetomidine 100 ?g / kg(0.1 mL / 10 g),and the other two groups were intraperitoneally injected with an equal volume of normal saline.At 24 h,use a fully automatic blood analyzer to measure the serum white blood cell count of mice and ELISA method to detect the concentration of TNF-?,IL-6 and HMGB1 in peritoneal tissue,and the pathological changes of the peritoneum were observed under a light microscope.Results Compared with the NS group,the white blood cell counts and the concentrations of TNF-?,IL-6 and HMBG1 in the peritoneal tissues increased in the AP group and Dex + Wort group(P(27)0.05).Compared with the AP group,the white blood cell count and the concentrations of TNF-?,IL-6 and HMGB1 in the peritoneal tissue of the Dex group were reduced(P(27)0.05),and the concentrations of TNF-? andIL-6 in the peritoneal tissue of the Dex + Wort group mice were reduced(P(27)0.05).Compared with the Dex group,the white blood cell count and the concentrations of TNF-?,IL-6 and HMGB1 in the peritoneal tissues increased(P(27)0.05).Under light microscope,the arrangement of cells in the peritoneal tissue of the Dex + Wort group was disordered,with moderate infiltration of inflammatory cells and bleeding in some tissues.Compared with the Dex group,the histopathological damage of the Dex +Wort group was worse.Conclusion Intraperitoneal injection of dexmedetomidine may inhibit the inflammatory response in mice with acute peritonitis through the PI3 K pathway.