A Comparative Study On The Anti-inflammatory And Analgesic Effects Of Intravenous And Intraperitoneal Injection Of Dexmedetomidine In Mice With Acute Peritonitis And Its Mechanism

Objective:Α possible mechanism of its anti-inflammatory effect was explored by observing the analgesic and anti-inflammatory effects of dexmedetomidine(DEX)intravenous injection and intraperitoneal injection on inflammatory visceral pain in mice with acute peritonitis.Methods:60 mice were divided into 5 groups by using rαndom number table method(n = 12): the blank control group(CK group),the acute peritonitis model group(VP group),the dexmedetomidine intravenous injection group(DEX-V group),the dexmetomidine intraperitoneal injection group(DEX-P group),and the dexmedetomidine + Methylamine group(DEX-M group).The VP group,DEX-V group,DEX-P group and DEX-M group established an acute peritonitis model by injecting acetic acid solution with density of 0.9%(0.1m L/10g)via intraperitoneal injection,whereas,the CK group was built up by injecting the same amout of normal saline via abdominal injection.In the first 15 min before the establishment of the model,the VP group,DEX-P group and DEX-M group were abdominal injected with saline,dexmedetomidine(10μg/kg),dexmedetomidine(10μg/kg)+methylamine(2.4μg/g),respectively.The DEX-V group was injected through the caudal vein with dextromidine(10μg/kg).The sedation and visceral pain behavior score(the VPI score)of each group were observed and recorded during the following 2h after the visceral pain model was established.After 6h since the model was established,the mice were harvested and executed,and the expression levels of IL-6 and TNF-α in the serum and peritoneum were obtained by Elisa method.Theperitoneal tissue in the abdominal cavity of the mice was selected and the degree of edema and the infiltration of neutrophils were observed undera light microscope.Results:Compared to the CK group,the VP group,DEX-V group and DEX-P group all responded with a torsion response,an increasing in VPI score,serum and peritoneal tissue homogenation of IL-6 and TNF-α(P<0.05),and an occur of different degrees of edema and neutrophilic infiltration in the peritoneal tissues.Compared with the VP group,the DEX-V group and the DEX-P group showeda better sedative effect after dexmeidine treatment,and a lower VPI score,serum and peritoneal tissue homogenate of IL-6 and the level(P<0.05),as well as a reduce in peritoneal tissue edema and neutrophil infiltration.There was no statistically significant difference among the experimental indexes of DEX-M group.Compared with the DEX-P group,the concentration of IL-6 and TNF-α in the homogenation of the peritoneal tissue of the DEX-V group increased(P<0.05).Similarly,the RASS score,VPI score,serum and peritoneal tissue homogenation of IL-6 and TNF-α also increased in DEX-M group(P<0.05).And at the same time,obvious increasing in the local peritoneal tissue edema and in neutrophilic infiltration were obtained.Conclusion : Both intravenous and intraperitoneal injection of dexmedetomidine can effectively reduce the inflammatory visceral pain of mice with acute peritonitis and have anti-inflammatory effect.Local injection is better than intravenous injection.Its anti-inflammatory mechanism is possibly related to the anti-inflammatory pathway of α7n ACh receptor activator cholinergic.