Objective To explore the effect of dexmedetomidine on the proliferation,invasion and cell cycle of gallbladder cancer cells by regulating the C-C chemokine ligand 2(CCL2)-C-C chemokine receptor 2(CCR2)pathway.Methods GBC-SD cells were devided into the control group,the low concentration dexmedetomidine group(2 μmol/L),the high concentration dexmedetomidine group(4 μmol/L)and the high concentration dexmedetomidine+CCL2 group(4 μmol/L dexmedetomidine and 10 μg/L CCL2 protein).The clone formation experiment and Edu experiment were performed to measure cell proliferation.Transwell experiment was performed to measure cell invasion and migration.Flow cytometry was performed to measure cell cycle and apoptosis.Western blot assay was used to measure the proliferating cell nuclear antigen(PCNA),Cyclin D1,matrix metalloproteinase(MMP)-2,MMP-9,Bcl-2 associated X protein(Bax),cysteine-dependent aspartate-specific protease-3(Caspase-3),CCL2 and CCR2 proteins.The nude mouse transplant tumor experiment was used to determine the growth of gallbladder cancer transplant tumors.Results After treatment with low and high concentrations of dexmedetomidine,the number of cell clone formed,the positive rate of Edu,the numbers of invasions and migrations,the expression levels of PCNA,CyclinD1,MMP-2,MMP-9,CCL2 and CCR2 proteins,the proportions of G2/M and S phase cells decreased,the proportion of G0/G1 phase cells,apoptosis rate and expression levels of Bax and Caspase-3 proteins increased,and the effect of high-concentration dexmedetomidine was more significant(P＜0.05).The inhibitory effects of dexmedetomidine on the proliferation,invasion,migration and cell cycle of gallbladder cancer cells,as well as its promoting effect on cell apoptosis could be reversed by CCL2 protein(P＜0.05).In vivo experiments showed that dexmedetomidine could reduce tumor mass,tumor volume of nude mice and expression levels of CCL2 and CCR2 proteins(P＜0.05).Conclusion Dexmedetomidine inhibits the proliferation and invasion of gallbladder cancer cells,and blocks the cell cycle in the G0/G1 phase by suppressing the CCL2-CCR2 pathway.

Objective To explore the effect of dexmedetomidine on the proliferation,invasion and cell cycle of gallbladder cancer cells by regulating the C-C chemokine ligand 2(CCL2)-C-C chemokine receptor 2(CCR2)pathway.Methods GBC-SD cells were devided into the control group,the low concentration dexmedetomidine group(2 μmol/L),the high concentration dexmedetomidine group(4 μmol/L)and the high concentration dexmedetomidine+CCL2 group(4 μmol/L dexmedetomidine and 10 μg/L CCL2 protein).The clone formation experiment and Edu experiment were performed to measure cell proliferation.Transwell experiment was performed to measure cell invasion and migration.Flow cytometry was performed to measure cell cycle and apoptosis.Western blot assay was used to measure the proliferating cell nuclear antigen(PCNA),Cyclin D1,matrix metalloproteinase(MMP)-2,MMP-9,Bcl-2 associated X protein(Bax),cysteine-dependent aspartate-specific protease-3(Caspase-3),CCL2 and CCR2 proteins.The nude mouse transplant tumor experiment was used to determine the growth of gallbladder cancer transplant tumors.Results After treatment with low and high concentrations of dexmedetomidine,the number of cell clone formed,the positive rate of Edu,the numbers of invasions and migrations,the expression levels of PCNA,CyclinD1,MMP-2,MMP-9,CCL2 and CCR2 proteins,the proportions of G2/M and S phase cells decreased,the proportion of G0/G1 phase cells,apoptosis rate and expression levels of Bax and Caspase-3 proteins increased,and the effect of high-concentration dexmedetomidine was more significant(P＜0.05).The inhibitory effects of dexmedetomidine on the proliferation,invasion,migration and cell cycle of gallbladder cancer cells,as well as its promoting effect on cell apoptosis could be reversed by CCL2 protein(P＜0.05).In vivo experiments showed that dexmedetomidine could reduce tumor mass,tumor volume of nude mice and expression levels of CCL2 and CCR2 proteins(P＜0.05).Conclusion Dexmedetomidine inhibits the proliferation and invasion of gallbladder cancer cells,and blocks the cell cycle in the G0/G1 phase by suppressing the CCL2-CCR2 pathway.

Objective To investigate the effect of sufentanil(ST)on lipopolysaccharide-induced acute lung injury(ALI)in rats by regulating the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)/stimulator of interferon gene(STING)signaling pathway.Methods Male SD rats were induced by lipopolysaccharide to construct an ALI model.The successfully modeled rats were randomly separated into ALI group,L-ST group,H-ST group,and H-ST+DMXAA group,with 6 rats in each group.Among them,the L-ST group and H-ST group were intraperitoneally injected with 2.5 μg/ml and 5 μg/ml ST after successful modeling immediately.The H-ST+DMXAA group was given 25 mg/kg DMXAA by gavage on the basis of intraperitoneal injection of 5 μg/ml ST.Six healthy and normal temperature rats were randomly selected as the control group,and an equal amount of physiological saline was injected intraperitoneally.The reagent kit was used to detect the SOD enzyme activity and MDA content in serum;ELISA was used to detect the levels of inflammatory factors such as interleukin-10(IL-10),tumor necrosis factor-α(TNF-α),and IL-6 in bronchoalveolar lavage fluid(BALF);cell staining was used to detect the total number of cells and neutrophils in BALF;the wet to dry mass ratio of lung tissue was calculated;HE staining was used to observe pathological changes in lung tissue,while Western blot was applied to detect the expression of cGAS and STING proteins in lung tissue.Results After L-ST and H-ST treatment,the SOD enzyme activity and IL-10 level increased sequentially,the MDA,TNF-α,IL-6,W/D value,total number of cells and neutrophils,cGAS,and STING protein expression decreased sequentially(P<0.05),while lung tissue injury was effectively alleviated.DMXAA reversed the influence of H-ST on the above indexes(P<0.05).Conclusion ST may inhibit the cGAS-STING pathway,reduce inflammation and oxidative stress responses,and thereby alleviates lipopolysaccharide induced ALI in rats.

Objective To investigate the effect of sufentanil(ST)on lipopolysaccharide-induced acute lung injury(ALI)in rats by regulating the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)/stimulator of interferon gene(STING)signaling pathway.Methods Male SD rats were induced by lipopolysaccharide to construct an ALI model.The successfully modeled rats were randomly separated into ALI group,L-ST group,H-ST group,and H-ST+DMXAA group,with 6 rats in each group.Among them,the L-ST group and H-ST group were intraperitoneally injected with 2.5 μg/ml and 5 μg/ml ST after successful modeling immediately.The H-ST+DMXAA group was given 25 mg/kg DMXAA by gavage on the basis of intraperitoneal injection of 5 μg/ml ST.Six healthy and normal temperature rats were randomly selected as the control group,and an equal amount of physiological saline was injected intraperitoneally.The reagent kit was used to detect the SOD enzyme activity and MDA content in serum;ELISA was used to detect the levels of inflammatory factors such as interleukin-10(IL-10),tumor necrosis factor-α(TNF-α),and IL-6 in bronchoalveolar lavage fluid(BALF);cell staining was used to detect the total number of cells and neutrophils in BALF;the wet to dry mass ratio of lung tissue was calculated;HE staining was used to observe pathological changes in lung tissue,while Western blot was applied to detect the expression of cGAS and STING proteins in lung tissue.Results After L-ST and H-ST treatment,the SOD enzyme activity and IL-10 level increased sequentially,the MDA,TNF-α,IL-6,W/D value,total number of cells and neutrophils,cGAS,and STING protein expression decreased sequentially(P<0.05),while lung tissue injury was effectively alleviated.DMXAA reversed the influence of H-ST on the above indexes(P<0.05).Conclusion ST may inhibit the cGAS-STING pathway,reduce inflammation and oxidative stress responses,and thereby alleviates lipopolysaccharide induced ALI in rats.