ABSTRACT
Objective To evaluate the effect of dexmedetomidine on pyroptosis during lung ischemia-reperfusion (I/R) in rats.Methods Adult male Sprague-Dawley rats,weighing 250-320 g,were used in this study.The model of isolated lung perfusion was established using an IL-2 Isolated Perfused Rat or Guinea Pig Lung System after the rats were anesthetized.Thirty lungs in which an ex vivo lung perfusion model was successfully established were divided into 3 groups (n=10 each) by a random number table method:control group (C group),I/R group and dexmedetomidine group (DEX group).The lungs were continuously perfused with K-H solution for 150 min in C group.After 15 min of perfusion,lungs were subjected to 60-min suspension of ventilation and perfusion,followed by 75 min of reperfusion and ventilation to establish the model of lung I/R injury in I/R and DEX groups.In DEX group,dexmedetomidine 10 nmol/L was added to K-H solution at the beginning of reperfusion.Lung tissues were obtained for determina-tion of wet/dry weight ratio (W/D ratio) and for examination of pathological changes (with a light microscope) and ultrastructure (using an electron microscope),and the alveolar damage rate (IAR) was calculated.The expression of pyroptosis-related factors including NOD-like receptor family protein 3 (NLRP3),caspase-1,interleukin-1β (IL-1β),IL-18 and gasdermin D (GSDMD) protein and mRNA was detected by Western blot or by real-time polymerase chain reaction.Results Compared with C group,the W/D ratio and IAR in lung tissues were significantly increased,and the expression of NLRP3,caspase-1,IL-1β,IL-18 and GSDMD protein and mRNA was up-regulated in I/R and DEX groups (P＜0.05).Compared with I/R group,the W/D ratio and IAR in lung tissues were significantly decreased,the expression of NLRP3,caspase-1,IL-1β,IL-18 and GSDMD protein and mRNA was down-regulated (P＜0.05),and the pathological changes were significantly attenuated in DEX group.Conclusion The mechanism by which dexmedetomidine reduces isolated rat lung I/R injury may be related to inhibiting pyroptosis.
ABSTRACT
Objective@#To evaluate the effect of dexmedetomidine on pyroptosis during lung ischemia-reperfusion (I/R) in rats.@*Methods@#Adult male Sprague-Dawley rats, weighing 250-320 g, were used in this study.The model of isolated lung perfusion was established using an IL-2 Isolated Perfused Rat or Guinea Pig Lung System after the rats were anesthetized.Thirty lungs in which an ex vivo lung perfusion model was successfully established were divided into 3 groups (n=10 each) by a random number table method: control group (C group), I/R group and dexmedetomidine group (DEX group). The lungs were continuously perfused with K-H solution for 150 min in C group.After 15 min of perfusion, lungs were subjected to 60-min suspension of ventilation and perfusion, followed by 75 min of reperfusion and ventilation to establish the model of lung I/R injury in I/R and DEX groups.In DEX group, dexmedetomidine 10 nmol/L was added to K-H solution at the beginning of reperfusion.Lung tissues were obtained for determination of wet/dry weight ratio (W/D ratio) and for examination of pathological changes (with a light microscope) and ultrastructure (using an electron microscope), and the alveolar damage rate (IAR) was calculated.The expression of pyroptosis-related factors including NOD-like receptor family protein 3 (NLRP3), caspase-1, interleukin-1β (IL-1β), IL-18 and gasdermin D (GSDMD) protein and mRNA was detected by Western blot or by real-time polymerase chain reaction.@*Results@#Compared with C group, the W/D ratio and IAR in lung tissues were significantly increased, and the expression of NLRP3, caspase-1, IL-1β, IL-18 and GSDMD protein and mRNA was up-regulated in I/R and DEX groups (P<0.05). Compared with I/R group, the W/D ratio and IAR in lung tissues were significantly decreased, the expression of NLRP3, caspase-1, IL-1β, IL-18 and GSDMD protein and mRNA was down-regulated (P<0.05), and the pathological changes were significantly attenuated in DEX group.@*Conclusion@#The mechanism by which dexmedetomidine reduces isolated rat lung I/R injury may be related to inhibiting pyroptosis.
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Objective To evaluate the effect of multimodal analgesia with diclofenac sodium on cognitive function following radical resection for colon cancer in elderly patients. Methods Sixty American Society of Anesthesiologists physical statusⅠorⅡpatients of either sex, aged 65-80 yr, weighing 45-85 kg, scheduled for elective open sigmoidectomy under general anesthesia, were divided into control group and test group by a random number table method with 30 patients in each group. In test group, diclofenac sodium suppository was administrated rectally before surgery and placed at about 2 to 3 cm above the anal dentate line, diclofenac sodium suppository 50 mg was given at 2 h before surgery and 4 h after surgery, followed by administration once every 12 h until 2 days after surgery. Patient-controlled intravenous analge-sia was performed after operation, dezocine 5 mg was intravenously injected when VAS score was more than 4 points within 48 h after surgery. The concentrations of serum interleukin-6 ( IL-6) , IL-8 and tumor nec-rosis factor-alpha ( TNF-α) were measured by enzyme-linked immunosorbent assay before surgery ( T0 ) and at 2, 6, 12, 24 and 48 h after surgery ( T1-5 ) . The postoperative requirement for rescue analgesia, post-operative analgesia satisfaction score, time of passing the first flatus and first postoperative off-bed time were recorded. Cognitive function was assessed at 1 day before surgery and 7 days after surgery, and the occur-rence of postoperative cognitive dysfunction was recorded. Results Compared with control group, the ser-um concentrations of IL-6 at T2-5 , IL-8 at T1-5 and TNF-αat T2-4 were significantly decreased, the require-ment for rescue analgesia and incidence of postoperative cognitive dysfunction were decreased, and the timeof passing the first flatus and first postoperative off-bed time were shortened in test group ( P<0. 05) . Con-clusion Diclofenac sodium for multimodal analgesia can improve cognitive function following radical resec-tion for colon cancer in elderly patients.
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Objective To investigate the effects of Dingkoulizhong decoction on cellular immune factors and adverse reactions in patients with advanced gastric cancer treated with chemotherapy.Methods One hundred and thirty-eight patients with advanced gastric cancer were enrolled in our hospital from October 2014to December 2016,and were randomly divided into control group (n =69) and observation group (n =69) by using the random number table.The patients of the control group were treated with FOLFOX4 chemotherapy (oxaliplatin + calcium folinate + fluorouracil),while the patients of the observation group were given by the treatment of Dingkoulizhong decoction on the basis of the control group.The peripheral blood samples of the patients were collected before and after the treatment.The levels of cellular immune factors CD3 +,CD4 +,CD8 + and CD4 +/CD8 + were detected,and the clinical efficacy and adverse reactions of the patients of the two groups were observed.Results After the treatment,the number of complete remission (CR),partial remission (PR),stable disease (SD) and progressive disease (PD) in the observation group were 16,25,16 and 12 cases respectively,while the control group were 9,20,19 and 21 cases respectively,and there was a statistically significant difference in the distribution of clinical efficacy between the two groups (Z =4.381,P =0.036).Compared with the control group,the clinical benefit rate (CBR) of the observation group was significantly improved (59.42％ vs.42.03％),with a statistically significant difference (x2 =4.175,P =0.041).The cellular immune factors CD3 + [(52.67 ±6.21)％ vs.(53.45 ±6.54)％],CD4 + [(23.56 ±3.85)％ vs.(24.09±2.91)％],CD8 +[(28.16±3.49)％ vs.(27.87±3.26)％] and CD4 +/CD8+(1.13 ± 0.27 vs.1.19 ±± 0.31) of the patients of the observation group showed no statistically significant difference (t=0.718,P=0.474;t=0.912,P=0.363;t=0.504,P=0.615;t=1.212,P=0.227) beforeand after the treatment,but the cellular immune factor CD3 + [(50.36 ± 3.74)％ vs.(53.13 ± 6.12)％],CD4 +[(21.26±2.37)％ vs.(23.44 ±3.96)％] andCD4+/CD8*(0.96±0.26vs.1.15±0.25) of the patients of the control group after the treatment were significantly lower than those before the treatment,and CD8 +[(31.64 ± 4.05) ％ vs.(27.98 ± 3.52) ％] after the treatment was significantly higher than that before the treatment,all with statistically significant differences (t =3.208,P ＜ 0.001;t =3.924,P ＜ 0.001;t =4.289P ＜ 0.001,t =5.666,P ＜ 0.001).Compared with the control group,the level of CD3 + [(53.45 ± 6.54) ％ vs.(50.36±±3.74)％],CD4+[(24.09±±2.91)％ vs.(21.26±2.37)％] andCD4+/CD8+(1.19±0.31vs.0.96 ± 0.26) of the patients of the observation group after the treatment were significantly improved,and CD8 +[(27.87 ± 3.26) ％ vs.(31.64 ± 4.05) ％] was significantly decreased,all with statistically significant differences (t=3.407,P=0.001;t =6.264,P＜0.001;t =4.722,P＜0.001;t =6.023,P＜0.001).Compared with the control group,the total adverse reaction rate of the observation group was significantly decreased (36.23％ vs.55.07％),with a statistically significant difference (x2 =4.936,P =0.026).Conclusion Dingkoulizhong decoction can significantly improve the clinical efficacy in patients with advanced gastric cancer treated with chemotherapy,alleviate the immune function damage caused by chemotherapy,and it can reduce the occurrence of adverse reactions.