升陷汤及单味药材水提物对缺氧/复氧致心肌损伤的保护作用

目的 通过观察升陷汤及单味药材水提物对离体培养的大鼠心肌细胞缺氧/复氧损伤的影响,并对其作用机制进行初步探讨。方法 培养H9C2大鼠心肌细胞,共分成8组：空白对照组,缺氧/复氧组（模型组）,缺氧复氧损伤后药物干预组（升陷汤全方及5个单味药材水提物组）。分别对心肌细胞凋亡率、心肌细胞的活力、细胞内活性氧（ROS）活性、细胞内钙离子浓度（Ca²⁺）等指标进行检测。结果 升陷汤全方及黄芪、知母等药材干预能明显降低细胞凋亡率、细胞内ROS活性和Ca²⁺浓度（P<0.05）,其中,全方的作用最强。与缺氧/复氧组细胞内ROS活性和Ca²⁺浓度增加至空白对照组的2.49倍及1.71倍相比,全方能使细胞内ROS活性和Ca²⁺浓度增加率降至缺氧/复氧组的41.37%和15.20%。结论 升陷汤及单味药材对缺氧/复氧致心肌损伤具有保护作用,该作用的机制可能通过抑制细胞凋亡、降低细胞内ROS以及Ca²⁺的浓度所致。     

nNOS抑制剂亚胺基烯丁基-L-鸟氨酸对心肌缺血再灌注损伤的影响及机制

目的 探讨nNOS选择性抑制剂亚胺基烯丁基-L-鸟氨酸（L-VNIO）对心肌缺血再灌注（I/R）损伤的影响及机制。方法 构建SD大鼠离体心脏I/R模型和H9c2细胞缺氧/复氧（H/R）模型；nNOS抑制剂L-VNIO（10 μmol·L^-1）持续给药整个再灌注或复氧过程。TTC染色测定心肌梗死面积；流式细胞术检测H9c2细胞凋亡率；Fluo-3/AM Ca²⁺荧光探针通过流式细胞仪检测H9c2细胞内Ca²⁺浓度；试剂盒法测定离体心脏灌流液乳酸脱氢酶（LDH）、丙二醛（MDA）水平以及H9c2细胞MDA水平和超氧化物歧化酶（SOD）活性；离体心脏提取肌浆网，试剂盒法检测肌浆网Ca²⁺-ATP酶（SERCA）活性，Western blotting检测肌浆网SERCA蛋白表达；Western blotting检测离体心脏中受磷蛋白（PLB）和兰尼碱受体2（RyR2）蛋白表达水平和磷酸化水平。结果 与I/R或H/R模型组相比，L-VNIO显著降低细胞凋亡率，减少心肌梗死面积，降低LDH、MDA水平，提高SOD活性，差异均有统计学意义（P<0.05）；此外，与I/R或H/R模型组相比，L-VNIO组明显降低细胞内Ca²⁺超载，增高PLB磷酸化水平，降低RyR2磷酸化水平，增强SERCA活性（P<0.05）。结论 nNOS抑制剂L-VNIO可以减轻I/R损伤，机制与调节Ca²⁺转运相关蛋白而降低I/R引起的Ca²⁺超载相关。     

圣草次苷激活Nrf2信号通路保护H9c2心肌细胞缺氧复氧损伤作用研究

目的 建立大鼠H9c2心肌细胞缺氧/复氧（H/R）损伤模型,考察圣草次苷改善心肌缺血再灌注损伤的作用机制。方法 利用无糖无血清培养基结合厌氧（94%N₂、5%CO₂、1%O₂）处理H9c2心肌细胞4h后,更换新鲜完全培养基再放入正常孵箱复氧24h,制备H/R损伤模型。在造模前12h给予圣草次苷（5、10、20μg·mL^-1）,细胞活力及乳酸脱氢酶（LDH）检测实验中选择灯盏乙素（20μg·mL^-1）作为阳性药,对照组及模型组给予等体积DMSO。MTT法测定细胞存活率;试剂盒检测细胞培养上清液中LDH水平;试剂盒检测细胞内丙二醛（MDA）水平和超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）活力;TUNEL染色检测细胞凋亡;DCFH-DA和JC-1探针分别检测细胞内活性氧（ROS）和线粒体膜电位改变;Western blotting检测核蛋白中转录因子（NF）-E2相关因子2（Nrf2）和总蛋白中血红素氧合酶1（HO-1）、γ-谷氨酰半胱氨酸连接酶（GCL）水平。结果 与对照组比较,H/R损伤诱导的模型组细胞存活率明显下降,凋亡明显增加,LDH水平明显升高,细胞内MDA水平明显升高,SOD、CAT、GSH-Px活力明显降低,ROS释放明显增多,线粒体膜电位明显降低,差异均有统计学意义（P＜0.01）;与模型组比较,圣草次苷可剂量相关性地改善上述变化,其中10、20μg·mL^-1组均差异显著（P＜0.01）。Western blotting结果显示,与对照组比较,模型组细胞Nrf2核转位以及HO-1、GCL表达水平无显著变化;与模型组比较,圣草次苷10、20μg·mL^-1显著增加Nrf2核转位及HO-1、GCL表达水平（P＜0.01）。结论 圣草次苷能够保护H/R诱导的H9c2心肌细胞损伤,其可能通过激活Nrf2抗氧化信号通路,增加细胞内源性抗氧化能力,抑制氧化应激损伤,保护线粒体功能以阻止细胞凋亡的发生。     

丹酚酸B预处理对心肌缺血/再灌注损伤能量代谢的影响

目的 观察丹酚酸B预处理对大鼠心肌缺血/再灌注损伤（MI/RI）能量代谢的作用。方法 通过结扎冠状动脉30min再灌注2 h建立大鼠MI/RI模型,随机分为4组：假手术组、模型组及丹酚酸B高、低（20、10 mg/kg）组,于建立模型前7 d开始ip给药,每天1次;再灌注结束后,采用比色法测定血清乳酸脱氢酶（LDH）、肌酸激酶（CK）活力,染色法测定心肌梗死面积（MIA）,定磷法测定心肌组织Na⁺-K⁺-ATP酶、Ca²⁺-Mg²⁺-ATP酶活性。结果 与模型组（42.60%）比较,丹酚酸B高、低剂量组的MIA分别缩小至35.93%和37.21%,差异显著（P<0.05）;与模型组比较,丹酚酸B高、低剂量组血清CK、LDH活力均显著降低（P<0.05、0.01）;与模型组比较,丹酚酸B高、低剂量组心肌组织Na⁺-K⁺-ATP酶、Ca²⁺-Mg²⁺-ATP酶活性均显著升高（P<0.05、0.01）。结论 丹酚酸B预处理可保护MI/RI所致心肌损伤,作用途径可能与改善心肌组织的能量代谢相关。     

诃子配伍铁棒锤对戊巴比妥钠诱导的H9c2心肌细胞毒效关系的影响及机制

目的 综合评价诃子(Terminalia chebula Retz.,TCR)-铁棒锤(Aconitum pendulum Busch.,APB)不同配比对H9c2心肌细胞毒效关系的影响,寻找两者的配比规律,并探究TCR-APB药对心肌的保护机制。方法 以APB为参照,按照1∶1,2∶1,3∶1及4∶1的比例配比TCR与APB药材并提取总提物,以戊巴比妥钠构建大鼠H9c2心肌细胞心力衰竭模型,计算4种配比总提物作用于H9c2心肌细胞的IC₅₀与EC₅₀值,比较其安全治疗指数(treatment indices,TI=IC₅₀/EC₅₀);并进一步探究TCR-APB药对H9c2心肌细胞活力、心肌指标[乳酸脱氢酶(lactate dehydrogenase,LDH)及肌酸激酶(creatine kinase,CK)]水平、线粒体膜电位(ΔΨ)、活性氧(reactive oxygen species,ROS)水平、钙离子(Ca²⁺)浓度及TRP基因、钙调节相关基因的mRNA水平。结果 TI计算结果显示,TCR与APB以2∶1比例配比时安全范围最好;100 ng·mL^–1的APB可显著上调TRPV1、TRPV2及TRPM8 mRNA水平,使TRPV4与TRPA1的mRNA水平显著下调,毒性浓度范围下的调节则相反;分子对接结果发现TRPM8对各成分的亲和力均比其他靶点强;最佳配比提取物及其活性单体均可显著提高细胞活力,改善戊巴比妥钠损伤导致的H9c2心肌细胞LDH渗漏、CK水平上升、ΔΨ降低、细胞内ROS水平上升、胞内Ca²⁺浓度增加以及FKBP1B和TRPM8的mRNA水平下调、RyR2和NOX2的mRNA水平上调等。结论 TCR与APB配伍均可缓解H9c2心肌细胞损伤,起到减毒增效的作用,其最佳配比为2∶1,二者配伍可以通过影响TRP基因,特别是TRPM8,调节肌质网中FKBP1B与RyR2基因以及线粒体中ROS水平,纠正Ca²⁺紊乱,从而保护心肌免受损伤。     

基于能量代谢分析白藜芦醇对H2O2诱导SH-SY5Y细胞保护作用

目的 基于能量代谢探究白藜芦醇对H2O2诱导的人神经母细胞瘤SH-SY5Y细胞氧化损伤的保护作用。方法 选取20、10、5、1 μmol•L^-1的白藜芦醇（Res）处理SH-SY5Y细胞24 h后,加入1.2 mmol•L^-1的H₂O₂,继续培养24 h,采用MTT法测定细胞活力,流式细胞术检测细胞凋亡率,试剂盒检测糖代谢相关酶己糖激酶（HK）、磷酸果糖激酶（PFK）、丙酮酸激酶（PK）、琥珀酸脱氢酶（SDH）、乳酸脱氢酶（LDH）活力以及葡萄糖消耗量、ATP含量,Western blot法检测低氧诱导因子1α（HIF-1α）和葡萄糖转运体1（GLUT-1）表达。结果 1.2 mmol•L^-1的H₂O₂造成SH-SY5Y细胞氧化损伤,细胞活力降低,细胞凋亡率升高（P<0.01）;与H₂O₂氧化损伤组相比,20、10、5 μmol•L^-1白藜芦醇组细胞活力升高,细胞凋亡率显著降低（P<0.01）;PFK、PK、SDH活力及ATP含量、葡萄糖消耗量显著升高,HK活力和细胞外LDH活力明显降低（P<0.01）;GLUT-1表达量显著升高,HIF-1α表达量显著降低（P<0.01）。结论 20、10、5 μmol•L^-1的白藜芦醇调控GLUT-1和HIF-1α蛋白表达,提高细胞糖代谢酶活力,增加产能,对H₂O₂诱导的SH-SY5Y细胞氧化损伤发挥保护作用。     

萝卜硫素调控JAK2/STAT3信号通路抑制缺血再灌注心肌细胞损伤的保护机制

目的 探讨萝卜硫素对新生大鼠心肌细胞缺血再灌注损伤（ischemia-reperfusion injury,IRI）的保护效应,并对其作用机制进行初步研究。方法 体外培养新生大鼠心肌细胞于缺氧24 h复氧1 h构建IRI细胞模型,观察细胞损伤情况;并将低、中、高剂量萝卜硫素（10,20,40 μg·ml^-1）及JAK2抑制剂（SAR302503）分别加入培养基中,与细胞共同处理24 h后,再置于上述缺氧复氧环境中培养,然后采用CCK8试剂盒检测萝卜硫素对心肌细胞增殖的影响,相关试剂盒检测萝卜硫素对细胞上清中乳酸脱氢酶（LDH）、丙二醛（MDA）、超氧化物歧化酶（SOD）含量的影响,免疫印迹检测萝卜硫素对细胞中JAK2/STAT3信号通路相关蛋白表达水平的影响。结果 与正常对照组相比,IRI组细胞相对存活率显著降低（P<0.05）,LDH及MDA含量显著升高（P<0.05）,而SOD活力则显著降低（P<0.05）,并且JAK2和STAT3磷酸化水平显著升高（P<0.05）;相对于IRI组而言,细胞经过不同浓度萝卜硫素及SAR302503处理后,细胞相对存活率显著升高（P<0.05）,LDH及MDA含量显著降低（P<0.05）,SOD活力则显著升高（P<0.05）,并且JAK2和STAT3磷酸化水平显著降低（P<0.05）。结论 萝卜硫素对缺血再灌注诱导的心肌细胞损伤具有保护作用,其作用机制可能与抑制JAK2/STAT3信号通路活化有关。     

云南鼠尾草提取物对大鼠H9c2心肌细胞缺氧/复氧损伤的保护作用

摘 要 目的：研究云南鼠尾草提取物对大鼠H9c2心肌细胞缺氧/复氧损伤保护作用的机制。方法: 建立大鼠H9c2心肌细胞缺氧/复氧损伤模型,并采用云南鼠尾草提取物进行干预。将体外培养的H9c2大鼠心肌细胞随机分为6组：正常对照（C）组、缺氧/复氧模型（H/R）组、缺氧/复氧模型+维拉帕米阳性对照（H/R+V）组、缺氧/复氧模型+云南鼠尾草低（H/R+L, 0.01 mg·L^-1）、中（H/R+M, 0.1 mg·L^-1）、高（H/R+H, 1.0 mg·L^-1）剂量组。采用噻唑蓝（MTT）法测定细胞存活率,利用检测试剂盒测定丙二醛（MDA）的含量和乳酸脱氢酶（LDH）的活性,通过荧光酶标仪测定荧光吸光度（A）值反映细胞内活性氧 （ROS）水平。结果: 与模型组比较,云南鼠尾草低、中、高剂量组均能显著提高心肌细胞存活率（P＜0.05或P＜0.01）,云南鼠尾草高剂量组显著减少细胞内LDH漏出量（P＜0.05或P＜0.01）、胞浆内MDA的含量（P＜0.01）和细胞内ROS水平（P＜0.05）。结论: 云南鼠尾草提取物对大鼠H9c2心肌细胞缺氧/复氧损伤具有保护作用,其相关作用机制可能与其减少脂质过氧化物和清除细胞氧自由基有关。     

狭基线纹香茶菜水溶性总黄酮对H2O2致LO2细胞损伤的保护作用

摘 要 目的：探讨狭基线纹香茶菜水溶性总黄酮(WSTF)对氧化应激损伤LO2细胞的保护作用。方法: 通过细胞毒性实验确定给药范围,建立过氧化氢（H2O2）致LO2细胞损伤模型,用含不同浓度WSTF的培养液与急性损伤肝细胞共孵育不同时间,采用MTT比色法测定细胞活力,检测谷氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST） 和丙二醛（MDA）的水平,评价WSTF对肝细胞损伤的保护作用。检测细胞线粒体膜电位和细胞内活性氧簇（ROS）水平,分析WSTF抑制H2O2诱导LO2细胞凋亡情况。结果:0.3 mmol·L^-1 H2O2处理LO2细胞4 h构建H2O2损伤LO2细胞模型,确定0.031 2~0.125 mg·mL^-1 WSTF为保护LO2细胞损伤的给药浓度范围。WSTF可抑制H2O2对肝细胞的损伤,并明显降低H2O2致急性损伤肝细胞的 ALT、AST 释放量和 MDA 水平,逆转H2O2诱导LO2肝细胞线粒体膜电位去极化和细胞内ROS升高。结论:WSTF体外给药对肝细胞损伤有保护作用。     

7-羟乙基白杨素对低压低氧致脑组织损伤的保护作用

目的 研究7-羟乙基白杨素（7-HEC）对低压低氧诱导大鼠脑组织损伤的保护作用。方法 将52只健康♂ Wistar大鼠随机分为正常组、模型组、乙酰唑胺组、7-HEC组，每组13只。连续灌胃给药5 d，末次给药后，除正常组，将其余3组置于低压低氧动物实验舱，升至8 000 m海拔缺氧处理24 h。HE染色观察脑组织病理改变，酶标法检测脑组织中过氧化氢（H₂O₂）和丙二醛（MDA）水平，以及超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）和ATP酶的活力；Western blotting检测蛋白B细胞淋巴瘤-2（Bcl-2）、Bcl-2相关X蛋白抗体（Bax）及半胱氨酸天冬氨酸特异性蛋白酶3（caspase-3）的表达。结果 与正常组相比，低压低氧导致大鼠脑组织出现明显损伤，H₂O₂和MDA水平显著升高，抗氧化酶SOD、CAT和GSH-Px以及Na⁺-K⁺-ATPase和Ca²⁺-Mg²⁺-ATPase的活力显著降低。7-HEC预处理能够逆转这些变化。此外，低压低氧能够显著升高脑组织中促凋亡蛋白Bax和cleaved caspase-3表达，降低抗凋亡蛋白Bcl-2的表达，而7-HEC能够下调Bax和cleaved caspase-3表达，上调Bcl-2的表达。结论 7-HEC对低压低氧致脑组织损伤具有明显的保护作用，其作用机制可能与其缓解氧化应激，抑制细胞凋亡，改善能量代谢有关。     

Taurine suppresses doxorubicin-triggered oxidative stress and cardiac apoptosis in rat via up-regulation of PI3-K/Akt and inhibition of p53, p38-JNK

The objective of the present study was to investigate the signaling mechanisms involved in the beneficial role of taurine against doxorubicin-induced cardiac oxidative stress. Male rats were administered doxorubicin. Hearts were collected 3 weeks after the last dose of doxorubicin and were analyzed. Doxorubicin administration retarded the growth of the body and the heart and caused injury in the cardiac tissue because of increased oxidative stress. Similar experiments with doxorubicin showed reduced cell viability, increased ROS generation, intracellular Ca²⁺ and DNA fragmentation, disrupted mitochondrial membrane potential and apoptotic cell death in primary cultured neonatal rat cardiomyocytes. Signal transduction studies showed that doxorubicin increased p53, JNK, p38 and NFκB phosphorylation; decreased the levels of phospho ERK and Akt; disturbed the Bcl-2 family protein balance; activated caspase 12, caspase 9 and caspase 3; and induced cleavage of the PARP protein. However, taurine treatment or cardiomyocyte incubation with taurine suppressed all of the adverse effects of doxorubicin. Studies with several inhibitors, including PS-1145 (an IKK inhibitor), SP600125 (a JNK inhibitor), SB203580 (a p38 inhibitor) and LY294002 (a PI3-K/Akt inhibitor), demonstrated that the mechanism of taurine-induced cardio protection involves activation of specific survival signals and PI3-K/Akt as well as the inhibition of p53, JNK, p38 and NFκB. These novel findings suggest that taurine might have clinical implications for the prevention of doxorubicin-induced cardiac oxidative stress.     

黄芩素-7-甲醚对缺氧致PC12细胞损伤的保护作用

目的 研究黄芩素-7-甲醚对缺氧PC12细胞的保护作用。方法 将PC12细胞分为正常对照组、缺氧模型组、芦丁组和黄芩素-7-甲醚组,培养24 h后,MTT法检测黄芩素-7-甲醚对细胞活力的影响;酶标仪法检测细胞培养上清液中乳酸脱氢酶（lactate dehydrogenase,LDH）活性以及细胞内丙二醛（malondialdehyde,MDA）、超氧化物歧化酶（superoxide dismutase,SOD）和过氧化氢酶（catalase,CAT）水平;2'',7''-二氯荧光素探针法检测细胞内活性氧簇（reactive oxygen species,ROS）水平;实时荧光定量PCR和Western blot检测核因子E2相关因子2（Nrf2）和血红素氧合酶-1（heme oxygenase-1,HO-1）的mRNA和蛋白的表达。结果 与正常对照组相比,缺氧导致PC12细胞活力显著降低,LDH、MDA和ROS水平显著升高,抗氧化酶SOD和CAT的活力显著降低。黄芩素-7-甲醚预处理能够逆转这些变化。此外,缺氧能够诱导细胞内Nrf2、HO-1的mRNA和蛋白表达增加,而黄芩素-7-甲醚能够进一步提高Nrf2、HO-1的mRNA和蛋白表达。结论 黄芩素-7-甲醚对缺氧致PC12细胞损伤有一定的保护作用,其作用机制可能与激活Nrf2/HO-1通路,抑制氧化应激损伤有关。     

Mechanisms underlying the protective effect of eugenol in rats with acute doxorubicin cardiotoxicity

The protective effect of eugenol and its possible mechanisms were investigated in rats with acute doxorubicin cardiotoxicity. Cardiac toxicity was induced by a single intraperitoneal injection of doxorubicin (20 mg/kg). Eugenol treatment (5 mg/kg/day, orally) was started 2 days before doxorubicin administration and continued for five consecutive days. Eugenol significantly reduced the elevated serum creatine kinase and lactate dehydrogenase levels, and restored the electrocardiographic disturbances resulted from doxorubicin administration. Also, eugenol reversed doxorubicin-induced deficits in the antioxidant defense mechanisms, decreased lipid peroxidation and attenuated the elevations in cytosolic Ca²⁺ and nitric oxide levels in cardiac tissue. In addition, doxorubicin-induced cardiac tissue damage observed by histopathological examination was markedly ameliorated with eugenol. Immunohistochemical analysis revealed that eugenol prevented the doxorubicin-induced activation of caspase-3 in cardiomyocytes. The cardioprotective effect afforded by eugenol was not significantly inhibited by prior administration of capsazepine, the transient potential vanilloid receptor-1 antagonist. It was concluded that eugenol, through its antioxidant activity and its ability to reduce cardiac Ca²⁺ accumulation and nitric oxide levels, is a potential candidate to protect against acute doxorubicin cardiotoxicity, a major and dose-limiting clinical problem.     

苦参碱对阿霉素诱导大鼠心肌损伤的保护作用及其机制研究

目的研究苦参碱对阿霉素诱导大鼠心肌损伤的保护作用及其机制。方法 SD大鼠随机分为对照组、模型组和苦参碱25、50、100 mg/kg组,每组各20只。模型组大鼠ip注射用阿霉素2.5 mg/kg,1次/周,连续给药6周,累积剂量15 mg/kg,建立心肌损伤模型。对照组ip等量生理盐水。苦参碱组造模前2 d ip注射用苦参碱25、50、100 mg/kg,连续给药5 d。观察大鼠心肌细胞病理学,采用酶联免疫吸附法检测大鼠血清线粒体偶联因子CF6水平,应用分光光度法测定Na~+-K~+-ATP酶、Ca2~+-ATP酶活力,采用试剂盒检测谷胱甘肽过氧化物酶(GSH-px)、总超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量。结果苦参碱各组心肌组织肿胀,肌束间、间质有灶性出血现象显著减轻。与模型组比较,苦参碱各组血清CF6水平显著降低(P0.05);线粒体Na~+-K~+-ATP酶、Ca2~+-ATP酶活性显著升高(P0.05);心肌组织GSH-px活性及SOD活力升高,MDA含量显著降低(P0.05)。结论苦参碱能保护阿霉素引起的大鼠心肌损伤,其作用机制与改善线粒体ATP酶活性、降低线粒体偶联因子6水平、减轻氧化应激水平有关。     

Salvianolic acid A displays cardioprotective effects in in vitro models of heart hypoxia/reoxygenation injury

Oxidative stress induced by overproduction of reactive oxygen species (ROS) plays an important role in hypoxia/reoxygenation (H/R) injury. In the present study, effects of salvianolic acid A (1) on heart H/R injury through its antioxidant activity were examined, using a molecule-based ROS scavenging system and cardiomyocyte model of H/R injury, as well as isolated rat heart model. As a result, 1 showed a potent antioxidant activity, scavenging all of the tested ROS and DPPH (2,2-diphenyl-1-picrylhydrazyl). The antioxidant effect of 1 was also observed in cardiomyocytes exposed to H/R. Compound 1 remarkably decreased dihydroethidium and dichlorofluorescein fluorescence and increased cell viability and mitochondrial membrane potential, ΔΨ_m, when compared to the H/R group. In isolated rat hearts exposed to H/R, 1 markedly increased the coronary flow, the peak of pressure development and the valley of pressure development, and significantly reduced the left ventricular end diastolic pressure when compared to the H/R group. These results suggested that 1 had significant protective effects against H/R-induced myocardial injury through its antioxidant activity.     

Protective effects of berberine against doxorubicin-induced cardiotoxicity in rats by inhibiting metabolism of doxorubicin

Abstract

1.?The clinical use of doxorubicin, an effective anticancer drug, is severely hampered by its cardiotoxicity. Berberine, a botanical alkaloid, has been reported to possess cardioprotective and antitumor effects. In this study, we investigated the cardioprotective effect of berberine on doxorubicin-induced cardiotoxicity and the effect of berberine on the metabolism of doxorubicin.

2.?Adult male Sprague-Dawley rats were administered doxorubicin in the presence or absence of berberine for 2 weeks. Administration of berberine effectively prevented doxorubicin-induced body weight reduction and mortality in rats.

3.?Berberine reduced the activity of myocardial enzymes, including aspartate aminotransferase (AST), creatine kinase (CK), CK isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Echocardiographic examination further demonstrated that berberine effectively ameliorated cardiac dysfunction induced by doxorubicin.

4.?Berberine inhibited the metabolism of doxorubicin in the cytoplasm of rat heart and reduced the accumulation of doxorubicinol (a secondary alcohol metabolite of doxorubicin) in heart.

5.?These data showed that berberine alleviated the doxorubicin-induced cardiotoxicity in rats via inhibition of the metabolism of doxorubicin and reduced accumulation of doxorubicinol selectively in hearts.     

Doxorubicin-induced vasomotion and [Ca^2＋]i elevation n vascular smooth muscle cells from C57BL/6 mice

Aim:

To explore the action of doxorubicin on vascular smooth muscle cells.

Methods:

Isometric tension of denuded or intact thoracic aortic vessels was recorded and [Ca²⁺]_i in isolated aortic smooth muscle cells was measured by using Fluo-3.

Results:

Doxorubicin induced phasic and tonic contractions in denuded vessels and increased levels of [Ca²⁺]_i in single muscle cells. Treatment with 10 μmol/L ryanodine had no effect on basal tension, but it did abolish doxorubicin-induced phasic contraction. Treatment with 10 mmol/L caffeine induced a transient phasic contraction only, and the effect was not significantly altered by ryanodine, the omission of extracellular Ca²⁺ or both. Phenylephrine induced rhythmic contraction (RC) in intact vessels. Treatment with 100 μmol/L doxorubicin enhanced RC amplitude, but 1 mmol/L doxorubicin abolished RC, with an increase in maximal tension. Caffeine at 100 μmol/L increased the frequency of the RC only. In the presence of 100 μmol/L caffeine, however, 100 μmol/L doxorubicin abolished the RC and decreased its maximal tension. Treatment with 10 μmol/L ryanodine abolished the RC, with an increase in the maximal tension. In Ca²⁺-free solution, doxorubicin induced a transient [Ca²⁺]_i increase that could be abolished by ryanodine pretreatment in single muscle cells. The doxorubicin-induced increase in [Ca²⁺]_i was suppressed by nifedipine and potentiated by ryanodine and charybdotoxin.

Conclusion:

Doxorubicin not only releases Ca²⁺ from the sarcoplasmic reticulum but also promotes the entry of extracellular Ca²⁺ into vascular smooth muscle cells.     

7-羟乙基白杨素对PC12细胞的抗氧化作用及机制研究

目的 研究7-羟乙基白杨素对PC12细胞的抗氧化作用，并对其保护机制进行探讨。方法 使用CCK-8试剂盒检测PC12细胞的存活率，筛选出7-羟乙基白杨素作用的最佳浓度进行实验。之后将PC12细胞随机分为4组，分别为对照组、缺氧组、白杨素组和7-羟乙基白杨素组。使用微量酶标法测定细胞培养基中LDH活性，DCFH-DA染色观察细胞内ROS含量，同时使用试剂盒对细胞内MDA、SOD和CAT水平进行测定，提取细胞总蛋白通过Western blotting检测评价Nrf2及其下游蛋白表达量。结果 缺氧后PC12细胞存活率显著下降，经7-羟乙基白杨素预处理后可获得改善；白杨素组和7-羟乙基白杨素组上清液中的LDH和细胞内ROS、MDA含量与缺氧组相比显著降低，SOD和CAT含量与缺氧组相比显著升高，同时发现7-羟乙基白杨素在各个方面的保护作用都明显强于白杨素。缺氧条件会使Nrf2、Keap1、HO-1、NQO1蛋白表达增加，7-羟乙基白杨素干预后可以进一步提高它们的蛋白表达。结论 7-羟乙基白杨素具有比白杨素更好的保护效果，它可以通过激活Nrf2/ARE通路减轻PC12细胞由于缺氧造成的损伤。     

Folic acid ameliorates celecoxib cardiotoxicity in a doxorubicin heart failure rat model

Context: The cardiotoxic effect of selective cyclo-oxygenase-2 inhibitors is well known. While rofecoxib and valdecoxib have been withdrawn, celecoxib remains on the market. Folic acid, a naturally occurring vitamin, has been shown to reduce myocardial ischemia and post-reperfusion injury in rats.

Objective: This study examined the cardiac effects of celecoxib and folic acid on doxorubicin-induced cardiomyopathy in rats.

Materials and methods: Cardiomyopathy was induced in male Wistar rats with six intraperitoneal injections of 2.5?mg/kg doxorubicin over a period of two weeks. The effect of 28?days of celecoxib (100?mg/kg/day) and its combination with folic acid (10?mg/kg/day) was studied on doxorubicin-induced cardiomyopathy according to serum lactate dehydrogenase (LDH), creatine kinase (CK-MB), troponin-T (Tn-T), tumor necrosis factor alpha (TNF-α), cardiac thiobarbituric acid reactive substance (TBARS), and glutathione (GSH) levels as well as systolic blood pressure (SBP), heart rate (HR) and ultrastructural studies.

Results: Celecoxib cardiotoxicity was manifested by significant increases in the LDH, Tn-T, TNF-α, CK-MB, SBP, HR (p?p?p?Discussion and conclusion: Folic acid protects against the cardiotoxic effects of celecoxib, which are aggravated in the presence of doxorubicin. Folic acid may act as a useful adjunct in patients who are taking celecoxib.