人工寒潮和热浪对易卒中型肾血管性高血压大鼠脑卒中的影响

doi:10.11817/j.issn.1673-9248.2023.03.008

目的

探讨人工寒潮和热浪对易卒中型肾血管性高血压大鼠（RHRSP）脑卒中发病的影响。

方法

健康雄性4~6周龄的SD大鼠随机分为实验组（24只）、假手术组（8只）和对照组（8只），实验组通过双肾双夹法建立RHRSP大鼠模型，将建模成功的24只RHRSP大鼠随机分为寒潮组、热浪组和正常气候组，每组各8只。利用RXZ-436A智能人工气候箱对实验组大鼠模拟寒潮、热浪和恒温恒湿天气，并在经历智能人工气候箱前后测量血压值并进行神经功能评分，3 d后处死各组大鼠并留取组织标本，首先观察有无脑出血情况，然后行TTC染色观察脑梗死情况，进行HE染色，观察脑组织病理学情况。采用重复测量方差分析和LSD检验比较对照组、假手术组和实验组大鼠在不同时间点（术前，术后4周，8周，12周）血压值的差异，采用单因素方差分析和LSD检验比较对照组、假手术组和实验组大鼠组间和实验组3亚组间在人工气候箱处理前后的血压值差异；采用配对t检验比较实验组大鼠组内人工气候箱处理前后的血压值的差异；采用χ²检验和Fisher精确检验分析各组大鼠脑卒中发病情况。

结果

实验组术后12周血压值大于术后8周、术后4周和术前[（196.63±18.40）mmHg vs（169.43±13.41）mmHg vs（143.80±6.63）mmHg vs（111.37±7.65）mmHg]，差异均具有统计学意义（P均＜0.05）。人工气候箱处理后，寒潮组血压大于正常气候组和热浪组[（225.40±19.29）mmHg vs（204.20±8.71）mmHg vs（188.68±10.01）mmHg]，差异具有统计学意义（P均＜0.05）。寒潮组组内人工气候箱处理后的血压大于处理前[（225.40±19.29）mmHg vs（204.22±18.74）mmHg]，热浪组处理后血压小于处理前[（188.68±10.01）mmHg vs（205.48±13.73）mmHg]，差异具有统计学意义（t=-2.789、3.586，P=0.027、0.009）。将寒潮组和热浪组合称为极端天气组，极端天气组中脑卒中发病大鼠8只，其中寒潮导致的脑梗死3只，脑出血2只，热浪导致的脑梗死2只，脑出血1只，正常气候组脑卒中发病大鼠0只，极端天气组大鼠脑卒中总发病数高于正常气候组，差异具有统计学意义（χ²=6.000，P=0.022）。

结论

人工寒潮和热浪可以增加RHRSP大鼠脑卒中的发病风险。

关键词: 寒潮, 热浪, 高血压, 脑卒中

Objective

To investigate the effects of artificial cold wave and artificial heat wave on stroke onset in stroke-prone medium-sized renal vascular hypertensive rats（stroke-prone renovascular hypertensive rats, RHRSP）.

Methods

Healthy male SD rats（4-6 weeks old) were randomly assigned into experimental group (n=24), sham-operated group (n=8), and control group (n=8). Twenty-four successfully modeled RHRSP rats were randomly assigned into cold wave group, heat wave group, and normal climate group, with 8 rats in each group. After 3 days, the rats in each group were executed and tissue specimens were collected to dete the presence of cerebral hemorrhage, then TTC staining was performed to observe the cerebral infarction, and HE staining was performed to detect the histopathology of the brain. Repeated measures analysis of variance and LSD test were used to compare the differences in blood pressure of rats in each group at different time points（before operation, 4 weeks, 8 weeks, and 12 weeks after operation). One-way analysis of variance and LSD test were used to compare the differences in blood pressure among groups of rats before and after artificial climate chamber treatment. Paired t test was used to compare the difference of blood pressure before and after treatment with artificial climate box in each group. Chi-square test and Fisher 's exact test were used to analyze the incidence of stroke in each group.

Results

The blood pressure value of the experimental group at 12 weeks after operation was higher than that at 8 weeks after operation, 4 weeks after operation, and before operation [(196.63±18.40) mmHg vs (169.43±13.41) mmHg vs (143.80±6.63) mmHg vs (111.37±7.65) mmHg], and the difference was statistically significant (P＜0.05). After the artificial climate chamber treatment, the blood pressure of the cold wave group was higher than that of the normal room temperature group, and the heat wave group [(225.40±19.29) mmHg vs (204.20±8.71) mmHg vs (188.68±10.01) mmHg], and there was a significant difference (P＜0.05 ). In the cold wave group, the blood pressure after artificial climate box treatment was higher than that before treatment [(225.40±19.29) mmHg vs (204.22±18.74) mmHg], and there was a significant difference (t=-2.789, P=0.027). In the heat wave group, the blood pressure after artificial climate box treatment was lower than that before treatment [(188.68±10.01) mmHg vs (205.48±13.73) mmHg] and there was a significant difference (t=3.586, P=0.009). The combination of cold and heat wave group was called the extreme weather group. There were 8 cases of stroke in the extreme weather group, including 3 cases of cerebral infarction caused by cold wave, 2 cases of cerebral hemorrhage, 2 cases of cerebral infarction caused by heat wave, 1 case of cerebral hemorrhage, and 0 cases in the normal climate group. The total number of stroke cases in the extreme weather group was significantly different from that in the normal climate group (χ²=6.000, P=0.022).

Conclusion

Artificial cold wave and heat wave can increase the risk of stroke in stroke-prone renovascular hypertensive rats with renal vascular hypertension.

Key words: Cold wave, Heat wave, Hypertensive, Stroke

表1 各组大鼠造模前后的血压比较（

x ¯

±s，mmHg）

组别	只数	术前	术后4周	术后8周	术后12周	F值	P值
对照组	8	110.74±4.55	112.22±5.59	114.17±7.18	116.62±7.41	0.896	0.453
假手术组	8	116.56±3.75	117.99±4.63	121.56±6.29	122.66±5.77	0.856	0.473
实验组	24	111.37±7.65	143.80±6.63^ab1	169.43±13.41^ab12	196.63±18.40^ab123	700.335	＜0.001
F值		2.161	107.744	99.748	125.515
P值		0.130	＜0.001	＜0.001	＜0.001

表1 各组大鼠造模前后的血压比较（

x ¯

±s，mmHg）

组别	只数	术前	术后4周	术后8周	术后12周	F值	P值
对照组	8	110.74±4.55	112.22±5.59	114.17±7.18	116.62±7.41	0.896	0.453
假手术组	8	116.56±3.75	117.99±4.63	121.56±6.29	122.66±5.77	0.856	0.473
实验组	24	111.37±7.65	143.80±6.63^ab1	169.43±13.41^ab12	196.63±18.40^ab123	700.335	＜0.001
F值		2.161	107.744	99.748	125.515
P值		0.130	＜0.001	＜0.001	＜0.001

表2 各组易卒中型肾血管性高血压模型大鼠人工气候箱处理前后的血压比较（

x ¯

±s，mmHg）

组别	只数	处理前	处理后	t值	P值
正常气候组	8	203.88±16.37	204.20±8.71	-0.048	0.963
寒潮组	8	204.22±18.74	225.40±19.29^a	-2.789	0.027
热浪组	8	205.48±13.73	188.68±10.01^ab	3.586	0.009
F值		0.021	14.881
P值		0.979	＜0.001

表2 各组易卒中型肾血管性高血压模型大鼠人工气候箱处理前后的血压比较（

x ¯

±s，mmHg）

组别	只数	处理前	处理后	t值	P值
正常气候组	8	203.88±16.37	204.20±8.71	-0.048	0.963
寒潮组	8	204.22±18.74	225.40±19.29^a	-2.789	0.027
热浪组	8	205.48±13.73	188.68±10.01^ab	3.586	0.009
F值		0.021	14.881
P值		0.979	＜0.001

图1 大鼠脑组织右侧额叶区可见脑出血灶　图2　大鼠脑组织TTC染色图。图a为正常大鼠脑组织，双侧均匀红色，图b为脑梗死大鼠脑组织，苍白色为梗死灶

图3 脑出血大鼠脑组织HE染色后可见轻度脑水肿，出血灶红细胞成团（图a：HE×100；图b：HE×200）图4　脑梗死大鼠脑组织病理图片。箭头所指右侧区域为脑梗死区，梗死灶内可见部分神经细胞消失，细胞间隙疏松，胞浆淡染，神经细胞出现核固缩、核碎裂或核溶解，多处出现空泡化（图a：HE×100；图b：HE×200）

图5 正常大鼠脑组织病理图片。组织细胞结构正常，细胞间隙均匀密集，细胞核居中清晰，胞浆丰富（图a：HE×100；图b：HE×200）图6　大鼠脑内动脉管壁病理图。图a示易卒中型肾血管性高血压模型大鼠脑内动脉管壁变性增厚，管腔狭窄，管周间隙增宽（HE×200）；图b示正常大鼠脑内动脉管壁平滑（HE×200）

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Effects of artificial cold and heat waves on stroke in stroke-prone renovascular hypertensive rats

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Effects of artificial cold and heat waves on stroke in stroke-prone renovascular hypertensive rats