依达拉奉预适应延长急性缺血性脑卒中溶栓时间窗的研究及ROS/TXNIP/NLRP3通路参与机制的探讨

doi:10.3877/cma.j.issn.2095-123X.2023.02.001

中华脑科疾病与康复杂志(电子版) ›› 2023, Vol. 13 ›› Issue (02) : 65 -74. doi: 10.3877/cma.j.issn.2095-123X.2023.02.001

基础研究

依达拉奉预适应延长急性缺血性脑卒中溶栓时间窗的研究及ROS/TXNIP/NLRP3通路参与机制的探讨

隆昱洲, 柳华, 张云茜, 李兴统, 范云虎, 尚正良, 宋镇妤, 罗丽华^†(

)

650021　昆明，云南大学附属医院神经内科
610014　成都市第三人民医院神经内科
650021　昆明，云南大学附属医院中心实验室

收稿日期:2022-02-23 出版日期:2023-04-15
通信作者: 罗丽华

Study on edaravone pretreatment prolonging thrombolytic time window by acute ischemic stroke and mechanism of ROS/TXNIP/NLRP3 pathway in rat

Yuzhou Long, Hua Liu, Yunqian Zhang, Xingtong Li, Yunhu Fan, Zhengliang Shang, Zhenyu Song, Lihua Luo^†()

Department of Neurology, Affiliated Hospital of Yunnan University, Kunming 650021, China
Department of Neurology, the Third People's Hospital of Chengdu, Chengdou 610014, China
Central Laboratory, Affiliated Hospital of Yunnan University, Kunming 650021, China

Received:2022-02-23 Published:2023-04-15
Corresponding author: Lihua Luo
Supported by:
the Applied Basic Research Joint Special Fund of Yunnan Provincial Science and Technology Department and Kunming Medical University(2019FE001 (-258)); Yunnan Provincial Health and Family Planning Commission Medical Discipline Leader Training Program Project(D-2017030)

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引用本文：

隆昱洲, 柳华, 张云茜, 李兴统, 范云虎, 尚正良, 宋镇妤, 罗丽华. 依达拉奉预适应延长急性缺血性脑卒中溶栓时间窗的研究及ROS/TXNIP/NLRP3通路参与机制的探讨[J/OL]. 中华脑科疾病与康复杂志(电子版), 2023, 13(02): 65-74.

Yuzhou Long, Hua Liu, Yunqian Zhang, Xingtong Li, Yunhu Fan, Zhengliang Shang, Zhenyu Song, Lihua Luo. Study on edaravone pretreatment prolonging thrombolytic time window by acute ischemic stroke and mechanism of ROS/TXNIP/NLRP3 pathway in rat[J/OL]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2023, 13(02): 65-74.

目的

探讨依达拉奉预处理对延长急性缺血性脑卒中（AIS）大鼠模型溶栓时间窗的影响及作用机制。

方法

选取健康SD大鼠64只随机分为假手术组、AIS组、重组组织型纤溶酶原激活剂（rt-PA）治疗组及rt-PA+依达拉奉治疗组，采用大鼠自体血栓构建AIS模型。采用Longa评分对各组大鼠在AIS后的神经功能进行评价，采用TTC染色法测定脑梗死体积，原位缺口末端标记观察大鼠脑内细胞凋亡的变化，酶联免疫吸附试验检测脑内活性氧（ROS）水平及超氧化物歧化酶（SOD）水平，硫代巴比妥酸检测脑内丙二醛（MDA）的含量，比色法检测脑内血红蛋白含量，Western blot实验检测ROS/TXNIP/NLRP3通路相关ASC、TXNIP、Caspase-1、IL-18和IL-1β的蛋白表达水平。

结果

rt-PA+依达拉奉治疗组在造模后6、7 h干预的大鼠的Longa评分较rt-PA治疗组降低，而且不同干预时间点的脑水肿程度和脑梗死体积改善情况均优于rt-PA治疗组，细胞凋亡率明显低于AIS组和rt-PA治疗组，差异具有统计学意义（P<0.05）。与rt-PA治疗组比较，rt-PA+依达拉奉治疗组在造模后7 h干预的大鼠ROS蛋白水平、MDA水平、血红蛋白含量均显著降低，在造模后7、8 h干预的大鼠SOD水平高于rt-PA治疗组，差异均具有统计学意义（P<0.05）。rt-PA治疗组及rt-PA+依达拉奉治疗组在造模后4.5 h干预的大鼠NLRP3、ASC、IL-18和IL-1β蛋白表达水平较AIS组下降，而且rt-PA+依达拉奉治疗组在造模后6、7 h的ASC、TXNIP、Caspase-1、IL-1β蛋白表达水平降低，差异均具有统计学意义（P<0.05）。与rt-PA治疗组比较，rt-PA+依达拉奉治疗组在造模后6 h干预的大鼠NLRP3的蛋白表达水平，造模后7 h的ASC、TXNIP蛋白表达水平，以及在造模后7、8 h的IL-18蛋白表达水平均降低，差异具有统计学意义（P<0.05）。

结论

依达拉奉预处理可以适当延长AIS大鼠rt-PA治疗的溶栓时间窗，其作用机制可能与ROS/TXNIP/NLRP3通路的参与有关。

关键词: 依达拉奉, 急性缺血性脑卒中, 大鼠, 脑血栓栓塞, 活性氧自由基

Objective

To investigate whether edaravone pretreatment can prolong the thrombolytic time window of acute ischemic stroke (AIS) rat model and its mechanism.

Methods

Sixty-four healthy SD rats were randomly divided into sham operation group, AIS group, recombinant tissue plasminogen activator (rt-PA) treatment group and rt-PA+edaravone treatment group. The AIS model was constructed by autologous thrombosis. The neurological function of rats in each group was evaluated after AIS, and the volume of cerebral infarction was measured by TTC method; Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling was used to observe the changes of cell apoptosis in rats; The levels of ROS and superoxide dismutase (SOD) in brain were detected by enzyme-linked immunosorbent assay; The content of malondialdehyde (MDA) in brain was detected by thiobarbituric acid; The content of hemoglobin in brain was detected by colorimetry; The content of hemoglobin in brain was measured by hemoglobin assay; The protein expression level of ASC, TXNIP, Caspase-1, IL-18 and IL-1β related to ROS/TXNIP/NLRP3 pathway were detected by Western blot.

Results

The Longa score of the rt-PA+edaravone treatment group was lower than that in the rt-PA treatment group after intravenous thrombolysis at 6 and 7 h, and the improvement of cerebral edema degree and cerebral infarction volume at different intervention time points were better than those in the rt-PA treatment group (P<0.05). The apoptosis rate was significantly lower than that in the AIS group and rt-PA treatment group, with a statistically significant difference (P<0.05). Compared with the rt-PA treatment group, the levels of ROS protein, MDA and hemoglobin of the rt-PA+edaravone treatment group after intravenous thrombolysis at 7 h were significantly reduced, and the SOD level after intravenous thrombolysis at 7 and 8 h were higher (P<0.05). The protein expression level of NLRP3, ASC, IL-18 and IL-1β of the rt-PA treatment group and rt-PA+edaravone treatment group after intravenous thrombolysis at 4.5 h were lower than those of AIS group, and the protein expression level of ASC, TXNIP, Caspase-1, IL-1 of rt-PA+edaravone treatment group after intravenous thrombolysis at 6 and 7 h were decreased (P<0.05). Compared with the rt-PA treatment group, the protein expression level of NLRP3 after intravenous thrombolysis at 6 h, the protein expression levels of ASC and TXNIP after intravenous thrombolysis at 7 h, and the protein expression level of IL-18 after intravenous thrombolysis at 7 and 8 h of the rt-PA+edaravone treatment group were decreased, with statistical significance (P<0.05).

Conclusion

Edaravone pretreatment can appropriately prolong the thrombolytic time window of rt-PA treatment in AIS rats, and its mechanism may be related to the participation of ROS/TXNIP/NLRP3 pathway.

Key words: Edaravone, Acute ischemic stroke, Rats, Cerebral thromboembolism, Reactive oxygen radical

表1 4组大鼠治疗前和不同溶栓时机干预12 h后的神经功能Longa评分比较（分，Mean±SE）

Tab.1 Comparison of Longa scores in 4 groups before treatment and after 12 h of intervention with different thrombolysis timing (score, Mean±SE)

组别	只数	治疗前	治疗12 h后
组别	只数	治疗前	4.5 h溶栓	6 h溶栓	7 h溶栓	8 h溶栓
AIS组	3	3.33±0.58	3.33±0.58	3.67±0.58	3.67±0.58	3.67±0.58
rt-PA治疗组	3	2.67±0.58	1.67±0.58^ab	2.00±0.00^ab	2.33±0.58^b	3.00±0.00
rt-PA+依达拉奉治疗组	3	2.33±0.58	1.67±0.58^ab	1.67±0.58^abc	2.00±0.00^abc	2.33±0.58^bc
F值		2.333	8.333	11.231	10.501	3.500
P值		0.178	0.019	0.007	0.011	0.098

表1 4组大鼠治疗前和不同溶栓时机干预12 h后的神经功能Longa评分比较（分，Mean±SE）

Tab.1 Comparison of Longa scores in 4 groups before treatment and after 12 h of intervention with different thrombolysis timing (score, Mean±SE)

组别	只数	治疗前	治疗12 h后
组别	只数	治疗前	4.5 h溶栓	6 h溶栓	7 h溶栓	8 h溶栓
AIS组	3	3.33±0.58	3.33±0.58	3.67±0.58	3.67±0.58	3.67±0.58
rt-PA治疗组	3	2.67±0.58	1.67±0.58^ab	2.00±0.00^ab	2.33±0.58^b	3.00±0.00
rt-PA+依达拉奉治疗组	3	2.33±0.58	1.67±0.58^ab	1.67±0.58^abc	2.00±0.00^abc	2.33±0.58^bc
F值		2.333	8.333	11.231	10.501	3.500
P值		0.178	0.019	0.007	0.011	0.098

图1 AIS后不同时间点TTC染色检测脑梗死体积

Fig.1 Cerebral infarction volume was detected by TTC staining at different time points after AIS

表2 4组大鼠于不同溶栓时机干预后脑含水量比较（%，Mean±SE）

Tab.2 Comparison of brain water content in 4 groups after intervention with different thrombolysis timing (%, Mean±SE)

溶栓时机	只数	假手术组	AIS组	rt-PA治疗组	rt-PA+依达拉奉治疗组	F值	P值
4.5 h	3	71.82±0.23	75.76±0.60^a	73.21±0.56^ab	73.04±0.29^ab	27.150	0.002
6 h	3	69.57±0.60	75.89±0.54^a	74.36±0.65^a	72.32±0.37^abc	49.751	<0.001
7 h	3	72.32±0.54	77.68±0.69^a	76.52±0.68^a	73.87±0.73^abc	24.923	<0.001
8 h	3	70.91±0.64	77.19±0.24^a	76.99±0.50^a	75.44±0.69^a	57.670	<0.001

表2 4组大鼠于不同溶栓时机干预后脑含水量比较（%，Mean±SE）

Tab.2 Comparison of brain water content in 4 groups after intervention with different thrombolysis timing (%, Mean±SE)

溶栓时机	只数	假手术组	AIS组	rt-PA治疗组	rt-PA+依达拉奉治疗组	F值	P值
4.5 h	3	71.82±0.23	75.76±0.60^a	73.21±0.56^ab	73.04±0.29^ab	27.150	0.002
6 h	3	69.57±0.60	75.89±0.54^a	74.36±0.65^a	72.32±0.37^abc	49.751	<0.001
7 h	3	72.32±0.54	77.68±0.69^a	76.52±0.68^a	73.87±0.73^abc	24.923	<0.001
8 h	3	70.91±0.64	77.19±0.24^a	76.99±0.50^a	75.44±0.69^a	57.670	<0.001

表3 4组大鼠于不同溶栓时机干预后相对梗死体积比较（%，Mean±SE）

Tab.3 Comparison of cerebral infarction volume in 4 groups after intervention with different thrombolysis timing (%, Mean±SE)

溶栓时机	只数	假手术组	AIS组	rt-PA治疗组	rt-PA+依达拉奉治疗组	F值	P值
4.5 h	3	2.55±0.27	27.38±2.91^a	20.11±2.13^ab	15.81±1.68^ab	54.781	<0.001
6 h	3	6.22±0.76	27.52±2.92^a	20.36±1.50^ab	15.43±0.88^abc	49.680	<0.001
7 h	3	3.74±0.43	27.13±2.88^a	25.23±2.68^a	15.55±1.65^abc	50.131	<0.001
8 h	3	4.56±0.48	36.42±1.49^a	32.12±0.79^ab	26.86±2.85^ab	140.901	<0.001

表3 4组大鼠于不同溶栓时机干预后相对梗死体积比较（%，Mean±SE）

Tab.3 Comparison of cerebral infarction volume in 4 groups after intervention with different thrombolysis timing (%, Mean±SE)

溶栓时机	只数	假手术组	AIS组	rt-PA治疗组	rt-PA+依达拉奉治疗组	F值	P值
4.5 h	3	2.55±0.27	27.38±2.91^a	20.11±2.13^ab	15.81±1.68^ab	54.781	<0.001
6 h	3	6.22±0.76	27.52±2.92^a	20.36±1.50^ab	15.43±0.88^abc	49.680	<0.001
7 h	3	3.74±0.43	27.13±2.88^a	25.23±2.68^a	15.55±1.65^abc	50.131	<0.001
8 h	3	4.56±0.48	36.42±1.49^a	32.12±0.79^ab	26.86±2.85^ab	140.901	<0.001

图2 4组大鼠于不同溶栓时机干预后脑细胞凋亡情况

Fig.2 Apoptosis of brain cells in 4 groups after intervention at different thrombolytic timing

表4 4组大鼠于不同溶栓时机干预后脑细胞凋亡率比较（%，Mean±SE）

Tab.4 Comparison of apoptosis of brain cells in 4 groups after intervention with different thrombolysis timing (%, Mean±SE)

溶栓时机	只数	假手术组	AIS组	rt-PA治疗组	rt-PA+依达拉奉治疗组	F值	P值
4.5 h	3	1.45±0.27	25.98±0.88^a	22.42±0.44^ab	18.67±1.88^abc	734.520	<0.001
6 h	3	1.58±0.17	30.34±1.13^a	23.01±0.15^ab	18.24±0.53^abc	609.243	<0.001
7 h	3	1.46±0.17	32.55±0.53^a	28.31±1.58^ab	19.10±0.28^abc	822.451	<0.001
8 h	3	1.48±0.04	41.06±0.84^a	37.00±1.07^ab	29.73±0.41^abc	403.672	<0.001

表4 4组大鼠于不同溶栓时机干预后脑细胞凋亡率比较（%，Mean±SE）

Tab.4 Comparison of apoptosis of brain cells in 4 groups after intervention with different thrombolysis timing (%, Mean±SE)

溶栓时机	只数	假手术组	AIS组	rt-PA治疗组	rt-PA+依达拉奉治疗组	F值	P值
4.5 h	3	1.45±0.27	25.98±0.88^a	22.42±0.44^ab	18.67±1.88^abc	734.520	<0.001
6 h	3	1.58±0.17	30.34±1.13^a	23.01±0.15^ab	18.24±0.53^abc	609.243	<0.001
7 h	3	1.46±0.17	32.55±0.53^a	28.31±1.58^ab	19.10±0.28^abc	822.451	<0.001
8 h	3	1.48±0.04	41.06±0.84^a	37.00±1.07^ab	29.73±0.41^abc	403.672	<0.001

图3 4组大鼠于不同溶栓时机干预后的脑组织氧化应激和血红蛋白含量比较A：MDA含量；B：ROS浓度；C：SOD浓度；D：血红蛋白浓度。与假手术组比较，^aP<0.05；与AIS组比较，^bP<0.05；与rt-PA组比较，^cP<0.05；AIS：急性缺血性脑卒中；rt-PA：重组组织型纤溶酶原激活剂

Fig.3 Comparison of oxidative stress and hemoglobin content in 4 groups after intervention with different thrombolysis timing

图4 ROS/TXNIP/NLRP3通路相关蛋白的表达水平

Fig.4 Expression levels of ROS/TXNIP/NLRP3 pathway-related proteins

表5 4组大鼠于不同溶栓时机干预后脑组织NLRP3蛋白的相对表达量比较（Mean±SE）

Tab.5 Comparison of relative expression of NLRP3 protein in 4 groups after intervention with different thrombolysis timing (Mean±SE)

组别	只数	4.5 h	6 h	7 h	8 h
假手术组	4	0.67±0.03	0.41±0.07	0.76±0.12	0.71±0.11
AIS组	4	1.42±0.07^a	1.51±0.20^a	1.10±0.11^a	1.15±0.11^a
rt-PA治疗组	4	1.01±0.02^ab	1.11±0.17^ab	1.03±0.11	1.11±0.10^a
rt-PA+依达拉奉治疗组	4	0.96±0.04^ab	0.82±0.11^abc	0.84±0.11	0.87±0.09
F值		85.910	19.920	3.808	8.706
P值		<0.001	<0.001	0.058	0.007

表5 4组大鼠于不同溶栓时机干预后脑组织NLRP3蛋白的相对表达量比较（Mean±SE）

Tab.5 Comparison of relative expression of NLRP3 protein in 4 groups after intervention with different thrombolysis timing (Mean±SE)

组别	只数	4.5 h	6 h	7 h	8 h
假手术组	4	0.67±0.03	0.41±0.07	0.76±0.12	0.71±0.11
AIS组	4	1.42±0.07^a	1.51±0.20^a	1.10±0.11^a	1.15±0.11^a
rt-PA治疗组	4	1.01±0.02^ab	1.11±0.17^ab	1.03±0.11	1.11±0.10^a
rt-PA+依达拉奉治疗组	4	0.96±0.04^ab	0.82±0.11^abc	0.84±0.11	0.87±0.09
F值		85.910	19.920	3.808	8.706
P值		<0.001	<0.001	0.058	0.007

表6 4组大鼠于不同溶栓时机干预后脑组织ASC蛋白的相对表达量比较（Mean±SE）

Tab.6 Comparison of relative expression of ASC protein in 4 groups after intervention with different thrombolysis timing (Mean±SE)

组别	只数	4.5 h	6 h	7 h	8 h
假手术组	4	0.54±0.03	0.54±0.09	0.80±0.13	0.56±0.08
AIS组	4	1.34±0.07^a	0.62±0.13	1.31±0.13^a	1.09±0.11^a
rt-PA治疗组	4	0.85±0.02^ab	0.75±0.12	1.20±0.13^a	1.06±0.09^a
rt-PA+依达拉奉治疗组	4	0.90±0.05^ab	0.74±0.11	0.88±0.12^bc	0.86±0.09^ab
F值		104.900	1.585	7.632	13.760
P值		<0.001	0.268	0.010	0.002

表6 4组大鼠于不同溶栓时机干预后脑组织ASC蛋白的相对表达量比较（Mean±SE）

Tab.6 Comparison of relative expression of ASC protein in 4 groups after intervention with different thrombolysis timing (Mean±SE)

组别	只数	4.5 h	6 h	7 h	8 h
假手术组	4	0.54±0.03	0.54±0.09	0.80±0.13	0.56±0.08
AIS组	4	1.34±0.07^a	0.62±0.13	1.31±0.13^a	1.09±0.11^a
rt-PA治疗组	4	0.85±0.02^ab	0.75±0.12	1.20±0.13^a	1.06±0.09^a
rt-PA+依达拉奉治疗组	4	0.90±0.05^ab	0.74±0.11	0.88±0.12^bc	0.86±0.09^ab
F值		104.900	1.585	7.632	13.760
P值		<0.001	0.268	0.010	0.002

表7 4组大鼠于不同溶栓时机干预后脑组织TXNIP蛋白的相对表达量比较（Mean±SE）

Tab.7 Comparison of relative expression of TXNIP protein in 4 groups after intervention with different thrombolysis timing (Mean±SE)

组别	只数	4.5 h	6 h	7 h	8 h
假手术组	4	0.69±0.06	0.44±0.07	0.52±0.09	0.66±0.09
AIS组	4	1.27±0.06^a	1.29±0.21^a	1.41±0.14^a	1.14±0.11^a
rt-PA治疗组	4	0.85±0.05	1.08±0.17^a	1.34±0.14^a	1.09±0.10^a
rt-PA+依达拉奉治疗组	4	0.87±0.05	0.81±0.11^ab	0.87±0.12^abc	0.89±0.09^ab
F值		35.780	11.890	22.840	9.686
P值		<0.001	0.003	<0.001	0.005

表7 4组大鼠于不同溶栓时机干预后脑组织TXNIP蛋白的相对表达量比较（Mean±SE）

Tab.7 Comparison of relative expression of TXNIP protein in 4 groups after intervention with different thrombolysis timing (Mean±SE)

组别	只数	4.5 h	6 h	7 h	8 h
假手术组	4	0.69±0.06	0.44±0.07	0.52±0.09	0.66±0.09
AIS组	4	1.27±0.06^a	1.29±0.21^a	1.41±0.14^a	1.14±0.11^a
rt-PA治疗组	4	0.85±0.05	1.08±0.17^a	1.34±0.14^a	1.09±0.10^a
rt-PA+依达拉奉治疗组	4	0.87±0.05	0.81±0.11^ab	0.87±0.12^abc	0.89±0.09^ab
F值		35.780	11.890	22.840	9.686
P值		<0.001	0.003	<0.001	0.005

表8 4组大鼠于不同溶栓时机干预后脑组织Caspase-1蛋白的相对表达量比较（Mean±SE）

Tab.8 Comparison of relative expression of Caspase-1 protein in 4 groups after intervention with different thrombolysis timing (Mean±SE)

组别	只数	4.5 h	6 h	7 h	8 h
假手术组	4	0.86±0.04	0.79±0.13	0.78±0.13	0.66±0.09
AIS组	4	1.20±0.06^a	1.42±0.17^a	1.17±0.11^a	1.15±0.11^a
rt-PA治疗组	4	1.07±0.06	1.17±0.18^a	1.08±0.12^a	1.09±0.10^a
rt-PA+依达拉奉治疗组	4	1.09±0.04	0.92±0.11^b	0.85±0.11^b	0.95±0.10^a
F值		15.39	6.715	4.901	9.337
P值		0.001	0.014	0.032	0.005

表8 4组大鼠于不同溶栓时机干预后脑组织Caspase-1蛋白的相对表达量比较（Mean±SE）

Tab.8 Comparison of relative expression of Caspase-1 protein in 4 groups after intervention with different thrombolysis timing (Mean±SE)

组别	只数	4.5 h	6 h	7 h	8 h
假手术组	4	0.86±0.04	0.79±0.13	0.78±0.13	0.66±0.09
AIS组	4	1.20±0.06^a	1.42±0.17^a	1.17±0.11^a	1.15±0.11^a
rt-PA治疗组	4	1.07±0.06	1.17±0.18^a	1.08±0.12^a	1.09±0.10^a
rt-PA+依达拉奉治疗组	4	1.09±0.04	0.92±0.11^b	0.85±0.11^b	0.95±0.10^a
F值		15.39	6.715	4.901	9.337
P值		0.001	0.014	0.032	0.005

表9 4组大鼠于不同溶栓时机干预后脑组织IL-18蛋白的相对表达量比较（Mean±SE）

Tab.9 Comparison of relative expression of IL-18 protein in 4 groups after intervention with different thrombolysis timing (Mean±SE)

组别	只数	4.5 h	6 h	7 h	8 h
假手术组	4	0.65±0.03	0.65±0.11	0.69±0.11	0.52±0.07
AIS组	4	1.30±0.07^a	1.37±0.29^a	1.22±0.12^a	1.35±0.13^a
rt-PA治疗组	4	0.89±0.06^ab	1.17±0.18^a	1.16±0.13^a	1.31±0.12^a
rt-PA+依达拉奉治疗组	4	0.92±0.07^ab	0.97±0.14^ab	0.83±0.11^bc	1.01±0.11^abc
F值		43	5.01	9.434	25.07
P值		<0.001	0.03	0.005	<0.001

表9 4组大鼠于不同溶栓时机干预后脑组织IL-18蛋白的相对表达量比较（Mean±SE）

Tab.9 Comparison of relative expression of IL-18 protein in 4 groups after intervention with different thrombolysis timing (Mean±SE)

组别	只数	4.5 h	6 h	7 h	8 h
假手术组	4	0.65±0.03	0.65±0.11	0.69±0.11	0.52±0.07
AIS组	4	1.30±0.07^a	1.37±0.29^a	1.22±0.12^a	1.35±0.13^a
rt-PA治疗组	4	0.89±0.06^ab	1.17±0.18^a	1.16±0.13^a	1.31±0.12^a
rt-PA+依达拉奉治疗组	4	0.92±0.07^ab	0.97±0.14^ab	0.83±0.11^bc	1.01±0.11^abc
F值		43	5.01	9.434	25.07
P值		<0.001	0.03	0.005	<0.001

表10 4组大鼠于不同溶栓时机干预后脑组织IL-1β蛋白的相对表达量比较（Mean±SE）

Tab.10 Comparison of relative expression of IL-1β protein in 4 groups after intervention with different thrombolysis timing (Mean±SE)

组别	只数	4.5 h	6 h	7 h	8 h
假手术组	4	0.78±0.04	0.57±0.09	0.47±0.08	0.64±0.09
AIS组	4	1.51±0.08^a	1.37±0.29^a	1.15±0.11^a	1.15±0.11^a
rt-PA治疗组	4	1.01±0.06^ab	1.11±0.17^a	0.87±0.09^ab	1.11±0.10^a
rt-PA+依达拉奉治疗组	4	1.05±0.10^ab	0.84±0.12^ab	0.76±0.10^ab	1.06±0.11^a
F值		33.740	6.966	16.670	10.570
P值		<0.001	0.013	<0.001	0.004

表10 4组大鼠于不同溶栓时机干预后脑组织IL-1β蛋白的相对表达量比较（Mean±SE）

Tab.10 Comparison of relative expression of IL-1β protein in 4 groups after intervention with different thrombolysis timing (Mean±SE)

组别	只数	4.5 h	6 h	7 h	8 h
假手术组	4	0.78±0.04	0.57±0.09	0.47±0.08	0.64±0.09
AIS组	4	1.51±0.08^a	1.37±0.29^a	1.15±0.11^a	1.15±0.11^a
rt-PA治疗组	4	1.01±0.06^ab	1.11±0.17^a	0.87±0.09^ab	1.11±0.10^a
rt-PA+依达拉奉治疗组	4	1.05±0.10^ab	0.84±0.12^ab	0.76±0.10^ab	1.06±0.11^a
F值		33.740	6.966	16.670	10.570
P值		<0.001	0.013	<0.001	0.004

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Study on edaravone pretreatment prolonging thrombolytic time window by acute ischemic stroke and mechanism of ROS/TXNIP/NLRP3 pathway in rat

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Study on edaravone pretreatment prolonging thrombolytic time window by acute ischemic stroke and mechanism of ROS/TXNIP/NLRP3 pathway in rat