1.Tetrahydrocurcumin protects against thoracic aortic aneurysm and dissection in mice by activating the SIRT3 signaling pathway
Xiangyan PENG ; Bin ZHANG ; Xinan QIAO ; He SUN ; Liqing JIANG ; Hanzhao ZHU ; Zhenxiao JIN ; Jincheng LIU ; Weixun DUAN
Acta Laboratorium Animalis Scientia Sinica 2025;33(3):311-323
Objective To investigate the protective effects and potential mechanisms of tetrahydrocurcumin(THC)on thoracic aortic aneurysm and dissection(TAAD)in mice.Methods TAAD was induced in 3-week-old C57BL/6J mice by oral administration of β-aminopropionitrile(BAPN)(diluted in drinking water,1 g/(kg·d)).Eighty mice were divided randomly into Con,BAPN,BAPN+THC,and BAPN+THC+3-TYP(SIRT3 inhibitor)groups(n=20 mice per group).The survival rate of mice in each group was recorded after 4 weeks.The maximum diameter of the aorta was measured and the histomorphology and aortic wall elastin integrity were evaluated by hematoxylin and eosin and elastin van Gieson staining.Macrophage infiltration was detected by immunohistochemical staining and α-smooth muscle actin(α-SMA)and osteopontin(OPN)expression were detected by immunofluorescence staining.The production of reactive oxygen species(ROS)was measured by dihydroethidium staining and superoxide dismutase(SOD)activity and malondialdehyde(MDA)levels were determined using kits.Protein expression levels of matrix metalloproteinase(MMP)2,MMP9,interleukin(IL)-6,tumor necrosis factor(TNF)-α,nuclear factor erythroid 2-related factor 2(NRF2),NADPH oxidase 2(NOX2),α-SMA,OPN,sirtuin 3(SIRT3),Ac-SOD2,and SOD2 were measured by Western Blot.Results Mice in the BAPN+THC group showed significantly higher survival and a lower incidence of TAAD compared with the BAPN group and the degree of aortic dilatation and morphology and structure were improved(P<0.05).Infiltration of CD68-positive macrophages and MMP2,MMP9,IL-6,and TNF-α expression levels were lower(P<0.05),ROS generation,MDA content,and NOX2 expression in aortic tissue were also significantly decreased,while SOD activity and NRF2 expression were increased(P<0.05).α-SMA expression was also increased,while OPN expression was reduced(P<0.05).SIRT3 expression was increased while the Ac-SOD2/SOD2 ratio was decreased(P<0.01).Treatment with the SIRT3-specific inhibitor and silencing of SIRT3 counteracted the ability of THC to resist TAAD via the SIRT3 signaling pathway(all P<0.05).Conclusions THC alleviated inflammation and oxidative stress in aortic tissues by activating the SIRT3 signaling pathway,thus inhibiting the phenotypic transformation of vascular smooth muscle cells and resisting the formation of TAAD in mice.
2.Tetrahydrocurcumin protects against thoracic aortic aneurysm and dissection in mice by activating the SIRT3 signaling pathway
Xiangyan PENG ; Bin ZHANG ; Xinan QIAO ; He SUN ; Liqing JIANG ; Hanzhao ZHU ; Zhenxiao JIN ; Jincheng LIU ; Weixun DUAN
Acta Laboratorium Animalis Scientia Sinica 2025;33(3):311-323
Objective To investigate the protective effects and potential mechanisms of tetrahydrocurcumin(THC)on thoracic aortic aneurysm and dissection(TAAD)in mice.Methods TAAD was induced in 3-week-old C57BL/6J mice by oral administration of β-aminopropionitrile(BAPN)(diluted in drinking water,1 g/(kg·d)).Eighty mice were divided randomly into Con,BAPN,BAPN+THC,and BAPN+THC+3-TYP(SIRT3 inhibitor)groups(n=20 mice per group).The survival rate of mice in each group was recorded after 4 weeks.The maximum diameter of the aorta was measured and the histomorphology and aortic wall elastin integrity were evaluated by hematoxylin and eosin and elastin van Gieson staining.Macrophage infiltration was detected by immunohistochemical staining and α-smooth muscle actin(α-SMA)and osteopontin(OPN)expression were detected by immunofluorescence staining.The production of reactive oxygen species(ROS)was measured by dihydroethidium staining and superoxide dismutase(SOD)activity and malondialdehyde(MDA)levels were determined using kits.Protein expression levels of matrix metalloproteinase(MMP)2,MMP9,interleukin(IL)-6,tumor necrosis factor(TNF)-α,nuclear factor erythroid 2-related factor 2(NRF2),NADPH oxidase 2(NOX2),α-SMA,OPN,sirtuin 3(SIRT3),Ac-SOD2,and SOD2 were measured by Western Blot.Results Mice in the BAPN+THC group showed significantly higher survival and a lower incidence of TAAD compared with the BAPN group and the degree of aortic dilatation and morphology and structure were improved(P<0.05).Infiltration of CD68-positive macrophages and MMP2,MMP9,IL-6,and TNF-α expression levels were lower(P<0.05),ROS generation,MDA content,and NOX2 expression in aortic tissue were also significantly decreased,while SOD activity and NRF2 expression were increased(P<0.05).α-SMA expression was also increased,while OPN expression was reduced(P<0.05).SIRT3 expression was increased while the Ac-SOD2/SOD2 ratio was decreased(P<0.01).Treatment with the SIRT3-specific inhibitor and silencing of SIRT3 counteracted the ability of THC to resist TAAD via the SIRT3 signaling pathway(all P<0.05).Conclusions THC alleviated inflammation and oxidative stress in aortic tissues by activating the SIRT3 signaling pathway,thus inhibiting the phenotypic transformation of vascular smooth muscle cells and resisting the formation of TAAD in mice.
3.Clinical analysis of short- and long-term complications after endoscopic Oddi's sphincterotomy in 95 patients
Ningli CHAI ; Jun WAN ; Benyan WU ; Changhao CAI ; Shiping XU ; Haitian HU ; Xinan QIAO ; Shuiping SUN ; Feng GAO ; Yunqing ZHU
Chinese Journal of Hepatobiliary Surgery 2010;16(9):659-663
Objective To investigate the short- and long-term complications after endoscopic Oddi's sphincterotomy (EST) upon endoscopic retrograde cholangiopancreatography (ERCP) procedure and determine whether the size of EST correlates to the occurrence of EST complications.Methods 95 cases receiving EST in the process of ERCP in our hospital were studied and followed up. The patients were divided into large, moderate and small incision groups according to the size of EST and the states of short-term and long-term EST complications were statistically analyzed.Results The incidence of short-term complications of EST was 18. 94% (18/95). They included bleeding in the process of ERCP in 11 cases, delayed bleeding in 3, acute pancreatitis in 1, acute cholangitis in 2 and duodenal perforation in 1. All these patients but 1 with duodenal perforation were discharged after undergoing symptomatic treatments. Eleven out of the 95 patients had long-term complications (11.57 % ). These included biliary system infection in 5 cases, recurrent calculus of bile duct in 3, papilla stricture in 1 and chronic relapsing pancreatitis in 2. All 11 patients recovered after therapeutic ERCP again or symptomatic drug treatments. There was no significant difference in incidence of short-term (χ2 =2.433, P=0.296) or long-term complications (χ2 = 1.151, P=0.562) among the 3 groups. Furthermore, there was no statistical correlation between the incision size of Oddi and complications including operative bleeding (P=0.109), short-term complications (P=0.124) and longterm complications(P=0.402). Conclusion There are many short-term and long-term complications after EST, but there is no correlation between the complications and the incision size of Oddi. The occurring rate of complications might be reduced through accurate direction of papilla incision, avoidance from injury of blood vessel, keeping bile drainage unobstructed and protection of the function of Oddi sphincter as far as possible in the process of ERCP.

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