百草枯中毒大鼠急性肺损伤机制及姜黄素的干预研究

doi:10.3877/cma.j.issn.1674-6880.2016.01.003

中华危重症医学杂志(电子版) ›› 2016, Vol. 09 ›› Issue (01) : 14 -19. doi: 10.3877/cma.j.issn.1674-6880.2016.01.003

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论著

百草枯中毒大鼠急性肺损伤机制及姜黄素的干预研究

何爱文¹, 陈寿权¹, 冷巧云², 刘玉荣³, 李惠萍¹^,^†(

), 李章平¹, 章杰¹, 薛继可¹, 雷远丽¹

^1. 325000　浙江温州，温州医科大学附属第一医院急诊科
^2. 332000　江西九江，九江市第一人民医院急诊科
^3. 519000　广东珠海，珠海市人民医院急诊科

收稿日期:2015-09-15 出版日期:2016-02-01
通信作者: 李惠萍
基金资助:
浙江省中医药科技计划项目(2010ZA082)

Mechanism of acute lung injury induced by paraquat and the intervention effect of curcumin in rats

Aiwen He¹, Shouquan Chen¹, Qiaoyun Leng², Yurong Liu³, Huiping Li¹^,^†(), Zhangping Li¹, Jie Zhang¹, Jike Xue¹, Yuanli Lei¹

^1. Department of Emergency, The First Affiliated Hosptal of Wenzhou Medical University, Wenzhou 325000, China
^2. Department of Emergency, Jiujiang No.1 People's Hospital, Jiujiang 332000, China
^3. Department of Emergency, Zhuhai People's Hospital, Zhuhai 519000, China

Received:2015-09-15 Published:2016-02-01
Corresponding author: Huiping Li
About author:
Corresponding author: Li Huiping, Email: wzlihuip@sina.com

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引用本文：

何爱文, 陈寿权, 冷巧云, 刘玉荣, 李惠萍, 李章平, 章杰, 薛继可, 雷远丽. 百草枯中毒大鼠急性肺损伤机制及姜黄素的干预研究[J]. 中华危重症医学杂志(电子版), 2016, 09(01): 14-19.

Aiwen He, Shouquan Chen, Qiaoyun Leng, Yurong Liu, Huiping Li, Zhangping Li, Jie Zhang, Jike Xue, Yuanli Lei. Mechanism of acute lung injury induced by paraquat and the intervention effect of curcumin in rats[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2016, 09(01): 14-19.

目的

探讨急性百草枯中毒大鼠肺组织氧化应激及脂质过氧化损伤机制及姜黄素的干预作用。

方法

将120只成年雄性SD大鼠按不同造模方法用随机数字表法分成对照组、百草枯中毒组、姜黄素干预组，每组大鼠40只。百草枯中毒组腹腔注射百草枯15 mg/kg，姜黄素干预组腹腔注射姜黄素200 mg/kg，15 min后腹腔注射百草枯15 mg/kg，对照组腹腔注射等容量的生理盐水。百草枯中毒组及姜黄素干预组于染毒后（对照组于腹腔注射后）3 h、6 h、24 h、3 d、7 d分别随机抽取8只大鼠取材。荧光实时定量PCR法测定各组大鼠肺组织中的转化生长因子（TGF）-β₁ mRNA的表达量，硫代巴比妥酸比色法、分光光度计比色法、黄嘌呤氧化酶法分别测定肺组织匀浆中丙二醛、髓过氧化物酶（MPO）、超氧化物歧化酶（SOD）活性，光镜下观察各组肺组织病理变化。

结果

染毒后6 h、24 h、3 d、7 d，与对照组相比，百草枯中毒组和姜黄素干预组肺组织TGF-β₁ mRNA的表达量明显升高（F = 136.928、32.282、52.008、30.940，P均< 0.05），丙二醛（F = 132.896、64.988、30.622、30.192）、MPO（F = 34.738、202.578、122.019、119.626）含量升高（P均< 0.05），而SOD活力降低（F = 34.738、202.578、122.019、119.626，P均< 0.05）；与百草枯中毒组相比，姜黄素干预组各时间点肺组织TGF-β₁ mRNA表达量、丙二醛及MPO含量均降低（P均< 0.05），肺组织SOD活力均升高（P均< 0.05）。

结论

氧化应激及细胞膜脂质过氧化过程的启动可能是百草枯中毒急性肺损伤的机制之一，姜黄素可能通过阻止该过程减轻肺损伤的程度。

关键词: 百草枯中毒, 氧化应激, 肺损伤, 姜黄素, 大鼠

Objective

To observe the oxidative stress and lipid peroxidation damage in lung of rats with acute paraquat (PQ) poisoning, and investigate the intervention effect of curcumin on it.

Methods

Totally 120 adult male Sprague-Dauley rats in the study were divided into the control, PQ-poisoned and curcumin-intervened groups (40 rats in each group). Rats in the PQ-poisoned group were intraperitoneally (i.p.) administered with PQ (15 mg/kg). Curcumin 200 mg/kg was injected i.p. at 15 min before administered with PQ (15 mg/kg, i.p.) in rats of the curcumin-intervened group. The same (15 mg/kg, i.p.) in rats of the curcumin-intervened group. The same volume of saline were injected i.p. in rats of the control group. Eight rats from each group were sacrificed at 3 h, 6 h, 24 h, 3 d, and 7 d after poisoning, respectively. The expression of TGF-β₁ mRNA in lungs of rats were measured with fluorescence real-time quantitative PCR. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), and superoxide dismutase (SOD) in lung of rats were measured with thiobarbituric acid colorimetric, spectrophotometer colorimetry and xanthine oxidase method, respectively. Pathological changes in lung were observed by light microscope.

Results

Compared with the control group, TGF-β1 mRNA expression in lung of rats increased significantly at 6 h, 24 h, 3 d, and 7 d after PQ poisoning (F = 136.93, 32.28, 52.01, 30.94; all P < 0.05), the levels of MDA (F = 132.896, 64.988, 30.622, 30.192) and MPO(F = 34.738, 202.578, 122.019, 119.626) increased obviously (all P < 0.05), but the SOD level decreased remarkably in the PQ-poisoned group and curcumin-intervened group (F = 34.738, 202.578, 122.019, 119.626; all P < 0.05). When compared with the PQ-poisoned group, the levels of TGF-β1 mRNA expression, MPO and MDA in lung of rats in the curcumin-intervened group decreased significantly and the level of SOD in the curcumin-intervened group increased statistically at 6 h, 24 h, 3 d, and 7 d after PQ poisoning (all P < 0.05).

Conclusions

The initiation of oxidative stress and lipid peroxidation of cell membrane may be one of the mechanisms of acute lung injury in rats with PQ poisoning. The curcumin may reduce the lung injury in rats by inhibiting it.

Key words: Paraquat poisoning, Oxidative stress, Lung injury, Curcumin, Rat

表1 各组40只大鼠不同时间点肺组织转化生长因子β1 mRNA表达量的比较（±s_）

组别	例数	3h	6 h	24 h	3 d	7d
对照组	8	1.01 ± 0.21	1.12 ± 0.19	1.11 ± 0.27	1.22 ± 0.18	1.31 ± 0.24
百草枯中毒组	8	1.67 ± 0.76	6.62 ± 0.63^a	3.10 ± 0.77^a	3.46 ± 0.47^a	8.43 ± 0.42^a
姜黄素干预组	8	1.14 ± 0.21	4.78 ± 0.97^ab	1.71 ± 0.33^ab	1.79 ± 0.61^ab	5.42 ± 0.87^ab
F值	?	4.406	136.928	32.282	52.008	30.940
P值	?	< 0.05	< 0.05	< 0.05	< 0.05	< 0.05

表1 各组40只大鼠不同时间点肺组织转化生长因子β1 mRNA表达量的比较（±s_）

组别	例数	3h	6 h	24 h	3 d	7d
对照组	8	1.01 ± 0.21	1.12 ± 0.19	1.11 ± 0.27	1.22 ± 0.18	1.31 ± 0.24
百草枯中毒组	8	1.67 ± 0.76	6.62 ± 0.63^a	3.10 ± 0.77^a	3.46 ± 0.47^a	8.43 ± 0.42^a
姜黄素干预组	8	1.14 ± 0.21	4.78 ± 0.97^ab	1.71 ± 0.33^ab	1.79 ± 0.61^ab	5.42 ± 0.87^ab
F值	?	4.406	136.928	32.282	52.008	30.940
P值	?	< 0.05	< 0.05	< 0.05	< 0.05	< 0.05

表2 各组40只大鼠不同时间点肺组织丙二醛活性的比较（nmol/mg，±s_）

组别	例数	3h	6 h	24 h	3 d	7d
对照组	8	6.34 ± 0.28	6.54 ± 0.32	6.19 ± 0.41	6.32 ± 0.31	6.28 ± 0.39
百草枯中毒组	8	7.34 ± 0.86	10.72 ± 0.33^a	11.43 ± 1.29^a	7.96 ± 0.55^a	8.82 ± 0.56^a
姜黄素干预组	8	6.33 ± 0.69	8.25 ± 0.76^ab	8.66 ± 0.84^ab	6.43 ± 0.51^b	7.34 ± 0.91^b
F值	?	6.244	132.896	64.988	30.622	30.192
P值	?	< 0.05	< 0.05	< 0.05	< 0.05	< 0.05

表2 各组40只大鼠不同时间点肺组织丙二醛活性的比较（nmol/mg，±s_）

组别	例数	3h	6 h	24 h	3 d	7d
对照组	8	6.34 ± 0.28	6.54 ± 0.32	6.19 ± 0.41	6.32 ± 0.31	6.28 ± 0.39
百草枯中毒组	8	7.34 ± 0.86	10.72 ± 0.33^a	11.43 ± 1.29^a	7.96 ± 0.55^a	8.82 ± 0.56^a
姜黄素干预组	8	6.33 ± 0.69	8.25 ± 0.76^ab	8.66 ± 0.84^ab	6.43 ± 0.51^b	7.34 ± 0.91^b
F值	?	6.244	132.896	64.988	30.622	30.192
P值	?	< 0.05	< 0.05	< 0.05	< 0.05	< 0.05

表3 各组40只大鼠不同时间点肺组织髓过氧化物酶活性的比较（U/g，±s_）

组别	例数	3h	6 h	24 h	3 d	7d
对照组	8	8.6 ± 0.9	8.8 ± 1.0	8.4 ± 0.9	8.3 ± 1.1	8.9 ± 0.9
百草枯中毒组	8	21.2 ± 2.8^a	32.2 ± 2.9^a	34.6 ± 3.9^a	27.3 ± 2.4^a	20.1 ± 1.9^a
姜黄素干预组	8	18.0 ± 2.7^ab	11.8 ± 1.3^ab	15.5 ± 2.4^ab	15.3 ± 3.4^ab	13.0 ± 1.5^ab
F值	?	6.566	34.738	202.579	122.019	119.626
P值	?	< 0.05	< 0.05	< 0.05	< 0.05	< 0.05

表3 各组40只大鼠不同时间点肺组织髓过氧化物酶活性的比较（U/g，±s_）

组别	例数	3h	6 h	24 h	3 d	7d
对照组	8	8.6 ± 0.9	8.8 ± 1.0	8.4 ± 0.9	8.3 ± 1.1	8.9 ± 0.9
百草枯中毒组	8	21.2 ± 2.8^a	32.2 ± 2.9^a	34.6 ± 3.9^a	27.3 ± 2.4^a	20.1 ± 1.9^a
姜黄素干预组	8	18.0 ± 2.7^ab	11.8 ± 1.3^ab	15.5 ± 2.4^ab	15.3 ± 3.4^ab	13.0 ± 1.5^ab
F值	?	6.566	34.738	202.579	122.019	119.626
P值	?	< 0.05	< 0.05	< 0.05	< 0.05	< 0.05

表4 各组40只大鼠不同时间点肺组织超氧化物歧化酶活性的比较（U/mg，±s_）

组别	例数	3h	6h	24 h	3d	7d
对照组	8	24.8 ± 1.2	25.2 ± 1.3	23.6 ± 1.2	22.9 ± 1.3	23.6 ± 1.1
百草枯中毒组	8	22.2 ± 1.5^a	14.8 ± 1.5^a	14.8 ± 0.8^a	18.6 ± 0.9^a	18.4 ± 0.8^a
姜黄素干预组	8	23.1 ± 1.3^a	22.9 ± 1.6^ab	23.0 ± 1.7^ab	21.6 ± 1.1^ab	20.6 ± 0.4^ab
F值	?	7.880	112.537	124.402	29.866	80.048
P值	?	< 0.05	< 0.05	< 0.05	< 0.05	< 0.05

表4 各组40只大鼠不同时间点肺组织超氧化物歧化酶活性的比较（U/mg，±s_）

组别	例数	3h	6h	24 h	3d	7d
对照组	8	24.8 ± 1.2	25.2 ± 1.3	23.6 ± 1.2	22.9 ± 1.3	23.6 ± 1.1
百草枯中毒组	8	22.2 ± 1.5^a	14.8 ± 1.5^a	14.8 ± 0.8^a	18.6 ± 0.9^a	18.4 ± 0.8^a
姜黄素干预组	8	23.1 ± 1.3^a	22.9 ± 1.6^ab	23.0 ± 1.7^ab	21.6 ± 1.1^ab	20.6 ± 0.4^ab
F值	?	7.880	112.537	124.402	29.866	80.048
P值	?	< 0.05	< 0.05	< 0.05	< 0.05	< 0.05

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Mechanism of acute lung injury induced by paraquat and the intervention effect of curcumin in rats

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Mechanism of acute lung injury induced by paraquat and the intervention effect of curcumin in rats