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全氟辛酸(perfluorooctanoic acid,PFOA)属于全氟类化合物,是全氟烷酸的重要代表物,其不仅具有较强的稳定性,还能耐光解、水解及微生物降解,基于此类特性PFOA被大量应用于食品包装、水源、纺织中,从而造成了广泛的环境污染,并为进入机体提供了条件;而饮食是摄入PFOA的主要途径,PFOA在机体中难被代谢排出[1-2]。研究[3-4]报道,在动物组织与人体血清中均能检测到PFOA,PFOA暴露会造成肝脏、心脏、肾脏、免疫、生殖及甲状腺等大量脏器系统侵损,是具有全身多脏器毒性作用的化合物。在心血管方面,PFOA可降低成年豚鼠心室肌细胞动作电位持续时间与峰值,此外可使膜电位改变异常,促进Ca2+内流加快细胞中Ca2+负荷从而发生心肌细胞损伤[5-6]。还有研究[6-7]发现,PFOA暴露在心脏中造成的心肌细胞损伤与氧化应激密切相关,PFOA暴露易增加活性氧释放,促进细胞DNA氧化加重心肌损伤程度。因此,目前应确定安全、有效药物用于预防PFOA引起的心肌损伤,显得尤为重要。
芦丁是一种生物活性丰富的黄酮类化合物,具有预防心肌缺血、心律失常,调节血清胆固醇等作用。研究[8-9]发现芦丁可缓解5-羟色胺所致的血管损伤并保护血管内皮细胞,同时还有抗炎症、抗化学性肝损伤的作用,但芦丁对PFOA造成的小鼠心肌损伤保护作用尚不明确。本研究探讨芦丁对PFOA诱导的小鼠心肌损伤的保护机制,为开发预防PFOA毒性作用心肌损伤的药物提供实验依据。
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各组小鼠体质量1~2 d比较差异无统计学意义(P>0.05);3~14 d各组小鼠体质量有差异,且PFOA组小鼠体质量低于PFOA+芦丁组(P < 0.05);PFOA组和PFOA+芦丁组小鼠干预14 d心脏质量低于对照组,而PFOA+芦丁组高于PFOA组(P < 0.05);3组小鼠14 d心脏体质量差异无统计学意义(P>0.05)(见表 1)。
分组 体质量D1 体质量D2 体质量D3 体质量D4 体质量D5 体质量D6 体质量D7 体质量D8 对照组 19.32±0.38 24.51±0.37 25.82±0.43 25.95±0.48 26.25±0.72 29.18±0.56 30.59±0.66 31.41±0.67 PFOA组 19.60±0.26 24.52±0.42 24.98±0.44* 25.02±0.45* 25.60±0.36* 26.80±0.45* 28.03±0.56* 27.96±0.52* PFOA+芦丁组 19.65±0.20 24.16±0.35 25.33±0.45* 25.91±0.54# 26.86±0.53*# 27.17±0.65*# 28.36±0.71 28.97±0.30*# F 3.01 2.32 7.35 9.06 10.26 41.94 37.14 93.34 P >0.05 >0.05 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 MS组内 0.084 0.145 0.194 0.242 0.310 0.313 0.418 0.270 分组 体质量D9 体质量D10 体质量D11 体质量D12 体质量D13 体质量D14 D14心脏质量/g D14心脏体质量比/% 对照组 32.73±0.83 33.60±0.80 34.01±0.91 34.59±0.86 35.53±0.89 36.01±0.93 0.65±0.02 1.81±0.38 PFOA组 27.67±0.72* 27.57±0.86* 26.51±0.63* 26.73±0.98* 27.61±0.99* 27.41±0.74* 0.48±0.02* 1.80±0.12 PFOA+芦丁组 28.20±0.66*# 28.45±0.74*# 28.79±0.93*# 29.07±0.76*# 29.89±0.57*# 29.76±0.62*# 0.58±0.01*# 1.95±0.36 F 113.01 132.12 169.83 171.62 190.21 263.93 194.71 0.59 P <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 >0.05 MS组内 0.548 0.642 0.697 0.760 0.699 0.599 0.000 0.096 q检验:与对照组比较*P < 0.05;与PFOA组比较#P < 0.05 表 1 芦丁干预PFOA暴露14 d小鼠体质量和心脏质量比较(ni=8;x±s; g)
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PFOA+芦丁组小鼠14 d心肌血清LDH活性低于PFOA组(P < 0.05);而PFOA组与PFOA+芦丁组小鼠14 d心肌TG、TC含量差异均无统计学意义(P>0.05)(见表 2)。
分组 TG含量/(mmol/L) TC含量/(mmol/L) LDH/(U/L) 对照组 3.17±0.44 2.36±0.56 194.91±88.13 PFOA组 3.81±0.68 3.24±0.51* 584.72±218.84* PFOA+芦丁组 2.61±1.35 2.96±0.23 485.09±168.40# F 2.18 4.84 7.32 P >0.05 <0.05 <0.01 MS组内 0.826 0.209 28 005.470 q检验:与对照组比较*P < 0.05;与PFOA组比较#P < 0.05 表 2 芦丁干预PFOA暴露14 d小鼠心肌TG、TC含量和血清LDH活性(ni=5;x±s)
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PFOA组小鼠14 d心肌MDA含量高于对照组(P < 0.05),而PFOA组与对照组小鼠14 d心肌T-SOD、GSH-PX活性差异无统计学意义(P>0.05);PFOA+芦丁组小鼠14 d心肌MDA含量低于PFOA组,但无统计学意义(P>0.05)。PFOA+芦丁组与PFOA组在小鼠14 d时心肌T-SOD活性上差异亦无统计学意义(见表 3)。
分组 T-SOD/(U/mg·prot) GSH-PX/(U/mg·prot) MDA/(nmol/mg·prot) 对照组 10 342.21±1 565.84 12 853.69±2 959.59 151.27±16.19 PFOA组 16 728.75±3 515.45 20 168.04±6 013.59 215.22±31.45* PFOA+芦丁组 15 366.38±11 288.74 26 208.19±10 713.66* 186.24±23.41 F 1.19 4.20 8.55 P >0.05 <0.05 < 0.01 MS组内 47 415 298.130 53 234 982.750 599.749 q检验:与对照组比较*P < 0.05;与PFOA组比较#P < 0.05 表 3 芦丁干预PFOA暴露14 d小鼠心肌MDA含量、GSH-PX和T-SOD活性(ni=5;x±s)
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对照组心肌纤维排列整齐,心肌细胞并未见萎缩或肥大;PFOA组小鼠表现出不同程度心肌细胞表现出肥大、坏死,心肌纤维扭曲、横纹模糊;如图中黑色箭头所示,PFOA处理组,部分心肌细胞胞核明显偏向细胞边缘。PFOA+芦丁组排列较为整齐,质内间观察到少量胶原纤维增生胞质,部分心肌细胞表现出心肌纤维扭曲轻微(见图 1)。
芦丁减轻全氟辛酸暴露致小鼠心肌损伤的作用研究
Effect of rutin on reducing myocardial injury induced by perfluorooctanoic acid exposure in mice
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摘要:
目的探讨芦丁对全氟辛酸(PFOA)造成的小鼠心肌损伤的保护作用研究。 方法采用PFOA暴露建立小鼠心肌损伤模型,观察芦丁对PFOA造成小鼠心肌损伤模型体质量、心脏质量、心肌TG、TC含量和血清LDH活性、氧化应激指标变化(心肌MDA含量、GSH-PX和T-SOD活性)及心肌组织形态学变化。 结果各组小鼠体质量1~2 d比较差异无统计学意义(P>0.05);3~14 d各组小鼠体质量有差异,且PFOA组小鼠体质量低于PFOA+芦丁组(P < 0.05);PFOA组和PFOA+芦丁组小鼠干预14 d心脏质量低于对照组,而PFOA+芦丁组高于PFOA组(P < 0.05)。PFOA组小鼠14 d心肌TC含量及血清LDH活性高于对照组(P < 0.05);PFOA+芦丁组小鼠14 d心肌TG含量及血清LDH活性低于PFOA组(P < 0.05);而PFOA组与PFOA+芦丁组小鼠14 d心肌TC含量差异无统计学意义(P>0.05);PFOA组小鼠14 d心肌MDA含量高于对照组(P < 0.05),而PFOA组与对照组小鼠14 d心肌T-SOD、GSH-PX活性差异无统计学意义(P>0.05);PFOA+芦丁组小鼠14 d心肌GSH-PX活性高于PFOA组,而PFOA+芦丁组与PFOA组在小鼠14 d时心肌MDA含量、GSH-PX活性差异无统计学意义(P>0.05)。 结论芦丁干预可以减轻PFOA暴露致小鼠心肌损伤作用。 Abstract:ObjectiveTo explore the protective effects of rutin on myocardial injury induced by perfluorooctanoic acid(PFOA) exposure in mice. MethodsPFOA was used to establish a model of myocardial injury in mice, and the effects of rutin on the body weight, heart weight, myocardial TG, TC content, serum LDH activity, and oxidative stress indicators(myocardial MDA content, GSH-PX and T-SOD activity) and myocardial morphology were investigated in mice. ResultsThere was no statistical significance in the weight of 1-2 d mice among all groups(P>0.05).The differences of in the weight of 3- 14 d mice on day 8 to day 14 among all groups were statistically significant(P < 0.05), and the weight of mice in PFOA group was lower than that in PFOA+rutin group, the heart weight of mice in PFOA group and PFOA+rutin group was lower than that in control group after 14 days of intervention, while the heart weight of mice in PFOA+rutin group was higher than that in PFOA group(P < 0.05).After 14 days of intervention, the myocardial TC content and serum LDH activity in PFOA group were higher than those in control group(P < 0.05), the myocardial TG content and serum LDH activity in PFOA+rutin group were lower than those in PFOA group(P < 0.05), and the difference of the myocardial TC content between PFOA group and PFOA+rutin group was not statistically significant(P>0.05).After 14 days of inverention, the myocardial MDA content and in PFOA group was higher than those in control group(P < 0.05), but there was no statistical significance in myocardial GSH-PX activity between PFOA group and the control group(P>0.05), the myocardial MDA content in PFOA+rutin group was lower than that in PFOA group, while the differences of the myocardial MDA content and GSH-PX activity between PFOA+rutin group and PFOA group were not statistically significant(P>0.05). ConclusionsRutin intervention can ameliorate the myocardial injury induced by PFOA exposure in mice. -
Key words:
- myocardial injury /
- rutin /
- perfluorooctanoic acid /
- toxicology
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表 1 芦丁干预PFOA暴露14 d小鼠体质量和心脏质量比较(ni=8;x±s; g)
分组 体质量D1 体质量D2 体质量D3 体质量D4 体质量D5 体质量D6 体质量D7 体质量D8 对照组 19.32±0.38 24.51±0.37 25.82±0.43 25.95±0.48 26.25±0.72 29.18±0.56 30.59±0.66 31.41±0.67 PFOA组 19.60±0.26 24.52±0.42 24.98±0.44* 25.02±0.45* 25.60±0.36* 26.80±0.45* 28.03±0.56* 27.96±0.52* PFOA+芦丁组 19.65±0.20 24.16±0.35 25.33±0.45* 25.91±0.54# 26.86±0.53*# 27.17±0.65*# 28.36±0.71 28.97±0.30*# F 3.01 2.32 7.35 9.06 10.26 41.94 37.14 93.34 P >0.05 >0.05 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 MS组内 0.084 0.145 0.194 0.242 0.310 0.313 0.418 0.270 分组 体质量D9 体质量D10 体质量D11 体质量D12 体质量D13 体质量D14 D14心脏质量/g D14心脏体质量比/% 对照组 32.73±0.83 33.60±0.80 34.01±0.91 34.59±0.86 35.53±0.89 36.01±0.93 0.65±0.02 1.81±0.38 PFOA组 27.67±0.72* 27.57±0.86* 26.51±0.63* 26.73±0.98* 27.61±0.99* 27.41±0.74* 0.48±0.02* 1.80±0.12 PFOA+芦丁组 28.20±0.66*# 28.45±0.74*# 28.79±0.93*# 29.07±0.76*# 29.89±0.57*# 29.76±0.62*# 0.58±0.01*# 1.95±0.36 F 113.01 132.12 169.83 171.62 190.21 263.93 194.71 0.59 P <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 >0.05 MS组内 0.548 0.642 0.697 0.760 0.699 0.599 0.000 0.096 q检验:与对照组比较*P < 0.05;与PFOA组比较#P < 0.05 表 2 芦丁干预PFOA暴露14 d小鼠心肌TG、TC含量和血清LDH活性(ni=5;x±s)
分组 TG含量/(mmol/L) TC含量/(mmol/L) LDH/(U/L) 对照组 3.17±0.44 2.36±0.56 194.91±88.13 PFOA组 3.81±0.68 3.24±0.51* 584.72±218.84* PFOA+芦丁组 2.61±1.35 2.96±0.23 485.09±168.40# F 2.18 4.84 7.32 P >0.05 <0.05 <0.01 MS组内 0.826 0.209 28 005.470 q检验:与对照组比较*P < 0.05;与PFOA组比较#P < 0.05 表 3 芦丁干预PFOA暴露14 d小鼠心肌MDA含量、GSH-PX和T-SOD活性(ni=5;x±s)
分组 T-SOD/(U/mg·prot) GSH-PX/(U/mg·prot) MDA/(nmol/mg·prot) 对照组 10 342.21±1 565.84 12 853.69±2 959.59 151.27±16.19 PFOA组 16 728.75±3 515.45 20 168.04±6 013.59 215.22±31.45* PFOA+芦丁组 15 366.38±11 288.74 26 208.19±10 713.66* 186.24±23.41 F 1.19 4.20 8.55 P >0.05 <0.05 < 0.01 MS组内 47 415 298.130 53 234 982.750 599.749 q检验:与对照组比较*P < 0.05;与PFOA组比较#P < 0.05 -
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