Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac dysfunction.Methods Specific pathogen-free chicken embryos(n=...Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac dysfunction.Methods Specific pathogen-free chicken embryos(n=120)were allocated untreated control,phosphate buffer solution(PBS)vehicle,PBS with ethanol vehicle,LPS(500 ng/egg),LPS with quercetin treatment(10,20,or 40 nmol/egg,respectively),Quercetin groups(10,20,or 40 nmol/egg).Fifteenday-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity.At embryonic day 19,the hearts of the embryos were collected for histopathological examination,RNA extraction,real-time polymerase chain reaction,immunohistochemical investigations,and Western blotting.Results They demonstrated that the heart presented inflammatory responses after LPS induction.The LPS-induced higher mRNA expressions of inflammation-related factors(TLR4,TNFα,MYD88,NF-κB1,IFNγ,IL-1β,IL-8,IL-6,IL-10,p38,MMP3,and MMP9)were blocked by quercetin with three dosages.Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of TLR4,IFNγ,MMP3,and MMP9 when compared with the LPS group.Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1,and significantly decreased protein expression of claudin 1 when compared with the LPS group.Quercetin significantly downregulated autophagyrelated gene expressions(PPARα,SGLT1,APOA4,AMPKα1,AMPKα2,ATG5,ATG7,Beclin-1,and LC3B)and programmed cell death(Fas,Bcl-2,CASP1,CASP12,CASP3,and RIPK1)after LPS induction.Quercetin significantly decreased immunopositivity to APOA4,AMPKα2,and LC3-II/LC3-I in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of AMPKα1,LC3-I,and LC3-II.Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.Conclusion Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy,programmed cell death,and myocardiocytes permeability.展开更多
BacKground Laparoscopic cholecystectomy has been widely used in clinical practice during the recent decades; however, the effects of pneumoperitoneum and the surgery on the coagulation system are largely unknown. This...BacKground Laparoscopic cholecystectomy has been widely used in clinical practice during the recent decades; however, the effects of pneumoperitoneum and the surgery on the coagulation system are largely unknown. This clinical study aimed to observe any possible effects of pneumoperitoneum and the surgery on the coagulation system of patients. Methods This was a prospective observational study. The inclusion criteria included (1) patients with chronic cholecystitis and/or cholecystic polyps and (2) patients in the relief stage of acute cholecystitis. The exclusion criteria included (1) patients in the episodic stage of acute cholecystitis and those complicated with cholangiolithiasis; (2) patients with concomitant hematologic diseases, damages to the liver function, malignant tumors or immune system diseases, or patients complicated with thrombotic or hemorrhagic disorders; and (3) patients who had taken anticoagulant medication within a week before surgery. Fifty patients who were hospitalized into our department for elective laparoscopic cholecystectomy between November 2011 and February 2013 were eligible and enrolled into this study. Of the 50 patients, 22 were male and 28 female. The age of the patients ranged from 29 to 78 (mean 56.7±11.5) years. The surgery for each of the 50 patients was performed with the same equipment and conditions. The surgeries for all the patients were performed under general anesthesia with the patients in a 30-degree head-up tilted posture, and the pressure of pneumoperitoneum was maintained at 13 mmHg. Venous blood specimens were taken from each patient before and at the end of pneumoperitoneum (i.e., 0 hour after surgery) and at 8 hours after surgery for determination of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), thrombin time (TT), and D-dimer (DD). The results of the determinations of these parameters were compared. Results (1) All the patients recovered well without any complications. (2) The pre-pneumoperitoneum values of the parameters of coagulation had normalized. (3) The PT values slightly increased (P 〉0.05) at the end of pneumoperitoneum (i.e., 0 hour after surgery) and decreased by 0.5 seconds at 8 hours after surgery as compared to the pre-pneumopedtoneum values (P 〈0.05). (4) APTT at 0 and 8 hours decreased by 1.4 seconds (P 〉0.05) and 3.7' seconds (P 〈0.05) respectively as compared to pre-pneumoperitoneum values, while the difference between the APTT values at 0 and 8 hours after surgery was not statistically significant (P 〉0.05). (5) FIB determined at 0 hour post-operation increased by 0.1 g/L as compared to pre-pneumoperitoneum values (P 〉0.05); however, the FIB values at 8 hours after operation increased by 1.2 g/L as compared to the pre-pneumoperitoneum values (P 〈0.05), and increased by 1.1 g/L as compared to 0 hour post-operation (P 〈0.05). (6) The TT values obtained at 0 and 8 hours post-operation were not significantly different as compared to the pre-pneumoperitoneum values (P 〉0.05). (7) The DD values gradually increased after operation; as compared to pre-pneumoperitoneum values, DD at 0 and 8 hours after operation increased by 210.8 ng/ml and 525.9 ng/ml respectively (P 〈0.05) and DD at 8 hours after operation increased by 315.1 ng/ml as compared to 0 hour post-operation (P 〈0.05). Conclusions The pneumoperitoneum for laparoscopic cholecycstectomy may lead to postoperative hypercoagulation in the patients, and thereby may increase the risks for development of postoperative thrombosis;Patients may have risks展开更多
基金supported by grants from the National Natural Science Foundation of China[No.32060819]。
文摘Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac dysfunction.Methods Specific pathogen-free chicken embryos(n=120)were allocated untreated control,phosphate buffer solution(PBS)vehicle,PBS with ethanol vehicle,LPS(500 ng/egg),LPS with quercetin treatment(10,20,or 40 nmol/egg,respectively),Quercetin groups(10,20,or 40 nmol/egg).Fifteenday-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity.At embryonic day 19,the hearts of the embryos were collected for histopathological examination,RNA extraction,real-time polymerase chain reaction,immunohistochemical investigations,and Western blotting.Results They demonstrated that the heart presented inflammatory responses after LPS induction.The LPS-induced higher mRNA expressions of inflammation-related factors(TLR4,TNFα,MYD88,NF-κB1,IFNγ,IL-1β,IL-8,IL-6,IL-10,p38,MMP3,and MMP9)were blocked by quercetin with three dosages.Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of TLR4,IFNγ,MMP3,and MMP9 when compared with the LPS group.Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1,and significantly decreased protein expression of claudin 1 when compared with the LPS group.Quercetin significantly downregulated autophagyrelated gene expressions(PPARα,SGLT1,APOA4,AMPKα1,AMPKα2,ATG5,ATG7,Beclin-1,and LC3B)and programmed cell death(Fas,Bcl-2,CASP1,CASP12,CASP3,and RIPK1)after LPS induction.Quercetin significantly decreased immunopositivity to APOA4,AMPKα2,and LC3-II/LC3-I in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of AMPKα1,LC3-I,and LC3-II.Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.Conclusion Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy,programmed cell death,and myocardiocytes permeability.
文摘BacKground Laparoscopic cholecystectomy has been widely used in clinical practice during the recent decades; however, the effects of pneumoperitoneum and the surgery on the coagulation system are largely unknown. This clinical study aimed to observe any possible effects of pneumoperitoneum and the surgery on the coagulation system of patients. Methods This was a prospective observational study. The inclusion criteria included (1) patients with chronic cholecystitis and/or cholecystic polyps and (2) patients in the relief stage of acute cholecystitis. The exclusion criteria included (1) patients in the episodic stage of acute cholecystitis and those complicated with cholangiolithiasis; (2) patients with concomitant hematologic diseases, damages to the liver function, malignant tumors or immune system diseases, or patients complicated with thrombotic or hemorrhagic disorders; and (3) patients who had taken anticoagulant medication within a week before surgery. Fifty patients who were hospitalized into our department for elective laparoscopic cholecystectomy between November 2011 and February 2013 were eligible and enrolled into this study. Of the 50 patients, 22 were male and 28 female. The age of the patients ranged from 29 to 78 (mean 56.7±11.5) years. The surgery for each of the 50 patients was performed with the same equipment and conditions. The surgeries for all the patients were performed under general anesthesia with the patients in a 30-degree head-up tilted posture, and the pressure of pneumoperitoneum was maintained at 13 mmHg. Venous blood specimens were taken from each patient before and at the end of pneumoperitoneum (i.e., 0 hour after surgery) and at 8 hours after surgery for determination of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), thrombin time (TT), and D-dimer (DD). The results of the determinations of these parameters were compared. Results (1) All the patients recovered well without any complications. (2) The pre-pneumoperitoneum values of the parameters of coagulation had normalized. (3) The PT values slightly increased (P 〉0.05) at the end of pneumoperitoneum (i.e., 0 hour after surgery) and decreased by 0.5 seconds at 8 hours after surgery as compared to the pre-pneumopedtoneum values (P 〈0.05). (4) APTT at 0 and 8 hours decreased by 1.4 seconds (P 〉0.05) and 3.7' seconds (P 〈0.05) respectively as compared to pre-pneumoperitoneum values, while the difference between the APTT values at 0 and 8 hours after surgery was not statistically significant (P 〉0.05). (5) FIB determined at 0 hour post-operation increased by 0.1 g/L as compared to pre-pneumoperitoneum values (P 〉0.05); however, the FIB values at 8 hours after operation increased by 1.2 g/L as compared to the pre-pneumoperitoneum values (P 〈0.05), and increased by 1.1 g/L as compared to 0 hour post-operation (P 〈0.05). (6) The TT values obtained at 0 and 8 hours post-operation were not significantly different as compared to the pre-pneumoperitoneum values (P 〉0.05). (7) The DD values gradually increased after operation; as compared to pre-pneumoperitoneum values, DD at 0 and 8 hours after operation increased by 210.8 ng/ml and 525.9 ng/ml respectively (P 〈0.05) and DD at 8 hours after operation increased by 315.1 ng/ml as compared to 0 hour post-operation (P 〈0.05). Conclusions The pneumoperitoneum for laparoscopic cholecycstectomy may lead to postoperative hypercoagulation in the patients, and thereby may increase the risks for development of postoperative thrombosis;Patients may have risks