Study of hemin in intermittent hypoxic rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LONG Shuzhen ¹ ^# , GAN Luoman ² ^# ,  LI Yu ² ,  LIU Guangnan ²

1. Guangxi Health Technical Vocational College, Nanning, Guangxi 530021, P. R. China;
2. Department of Respiratory Medicine, Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530022, P. R. China;

Corresponding author：

LI Yu, Email: 13471017279@163.com; LIU Guangnan, Email: 1821858774@qq.com

Keywords：

Intermittent hypoxia; Hemin; Hypertension; Endogenous carbon monoxide; Heme oxygenase-1

DOI：

10.7507/1671-6205.201804044

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Objective To study the influence of hemin on blood pressure of intermittent hypoxic rats and investigate the mechanism of hypertension caused by intermittent hypoxia.Methods Twenty-four male SD rats were randomly divided into a hemin group, an intermittent hypoxia group (IH group) and a normal group. Thirty minutes after intraperitoneal injection of hemin, the rats in the hemin group were exposed to intermittent normobaric hypoxic environment (8 h/d). The rats in the IH group were intraperitoneal injected with normal sodium and then exposed to the same environment (8 h/d). The rats in the normal group were intraperitoneal injected with normal sodium and placed in the glass box. The three groups were bred in the same condition. Thirty-five days later, the mean carotid artery pressure (mCAP) of the rats was measured and their plasma carbon monoxide (CO) level was measured by Chalmer’s method. Reverse transcription polymerase chain reaction was performed to detect the levels of heme oxygenase-1 (HO-1) mRNA expression in lung, liver, spleen, kidney and other organs. The expression of HO-1 protein in the organs was detected by immunohistochemistry.Results The mCAP in the IH group was significantly higher than the hemin group and the normal group (P<0.05), and was higher in the hemin group than the normal group (P<0.05). The concentration of plasma CO in the hemin group was higher than the IH group and the normal group (P<0.05). There was no significant difference in plasma CO between the IH group and the normal group (P>0.05). The expression of HO-1 mRNA of lung, liver, spleen and kidney in the hemin group and the IH group was higher than the normal group (P<0.05), and was higher in the hemin group than the IH group (P<0.05). The relationship between mCAP and HO-1 mRNA showed a curvilinear trend. The quadratic curve fitting equation was Y=39.715+446.640X-334.353X².Conclusions Intermittent hypoxia can cause hypertension in rats. The HO-1 expression is increased in hypoxic rats, but the plasma CO does not increase significantly. As an inducer of HO-1, hemin can increase the expression of HO-1 and CO in hypoxic rats, then lower their blood pressure to some extent.

Citation： LONG Shuzhen, GAN Luoman, LI Yu, LIU Guangnan. Study of hemin in intermittent hypoxic rats. Chinese Journal of Respiratory and Critical Care Medicine, 2019, 18(1): 31-36. doi: 10.7507/1671-6205.201804044 Copy

1.	朱小川, 储德节, 洪燕, 等. 阻塞性睡眠呼吸暂停低通气综合征与高血压的相关性及危险因素分析. 中国临床医学, 2015, 11(6): 750-753.
2.	刘旺, 彭敏, 刘土轩, 等. 不同程度的 OSAHS 合并高血压患者在不同时间段的血压水平对比观察. 中国实用医药, 2017, 12(30): 40-41.
3.	王维维, 英俊岐, 高春燕, 等. 阻塞性睡眠呼吸暂停低通气综合征与老年高血压的相关性. 中国地方病防治杂志, 2017, 32(7): 730-731.
4.	陈宝元, 何权瀛. 重视睡眠呼吸暂停相关性高血压的诊断和防治. 中华医学杂志, 2009, 89(26): 1801-1803.
5.	梁瑞玲, 任寿安. 阻塞性睡眠呼吸暂停合并高血压发病机制研究进展. 中华高血压杂志, 2018, 26(3): 288-291.
6.	盛红宇, 姚晓光, 木拉力别克, 等. 短期持续正压通气治疗对不同性别 OSAHS 合并高血压患者降压疗效的比较. 中华全科医学, 2016, 14(1): 9-11.
7.	徐小华, 韩志强, 田明庆, 等. 高血压合并阻塞性睡眠呼吸暂停低通气综合征患者持续气道正压通气治疗前后血压与血管紧张素水平的研究. 浙江中医药大学学报, 2014, 38(5): 595-597.
8.	李黎, 王怀振, 杨晓红, 等. 持续气道正压通气在 OSAHS 合并高血压患者中的疗效评价. 中国医药科学, 2014, 4(21): 9-11.
9.	Kanagy NL, Walker BR, Nelin LD. Role of endothelin in intermittent hypoxia-induced hypertension. Hypertension, 2001, 37(2 Pt 2): 511-515.
10.	Fletcher EC. Physiological consequences of intermittent hypoxia: systemic blood pressure. J Appl Physiol, 2001, 90(4): 1600-1605.
11.	罗荧荃, 黄国庆, 杨宇. 慢性间歇低氧诱发大鼠高血压模型的建立. 中国新药杂志, 2006, 15(22): 1930-1933.
12.	吴晓丹, 黄建浩, 孔德红, 等. 慢性间歇低氧大鼠模型的建立和超声心动图评价. 复旦学报(医学版), 2011, 38(6): 481-484.
13.	蒋丽君, 刘建红, 宋玮, 等. 慢性间歇低氧并高血压 SD 大鼠模型的建立. 中国临床新医学, 2015, 8(11): 1013-1015.
14.	Chalmers AH. Simple, sensitive measurement of carbon monoxide in plasma. Clin Chem, 1997, 37(8): 1442-1445.
15.	申洪. 免疫组织化学染色定量方法研究. 中国组织化学与细胞化学杂志, 1995, 4(1): 89-91.
16.	Ndismag JF, Wang R. Age-related alterations in soluble guanylyl cyclase and cGMP pathway in spontaneously hypertensive rats. J Hypertens, 2003, 21(6): 1117-1124.
17.	李瑞珍. Hemin 对妊娠期高血压疾病大鼠 HO-1 的表达、血压及尿蛋白的影响[D]. 湖南: 中南大学湘雅三医院, 2014, 1-2.
18.	李玉明, 郑新程, 刘俊昌, 等. LPS 对培养的大鼠主动脉平滑肌细胞 HO-1 表达的影响. 中国病理生理杂志, 2000, 16(10): 1012-1013.

1. 朱小川, 储德节, 洪燕, 等. 阻塞性睡眠呼吸暂停低通气综合征与高血压的相关性及危险因素分析. 中国临床医学, 2015, 11(6): 750-753.
2. 刘旺, 彭敏, 刘土轩, 等. 不同程度的 OSAHS 合并高血压患者在不同时间段的血压水平对比观察. 中国实用医药, 2017, 12(30): 40-41.
3. 王维维, 英俊岐, 高春燕, 等. 阻塞性睡眠呼吸暂停低通气综合征与老年高血压的相关性. 中国地方病防治杂志, 2017, 32(7): 730-731.
4. 陈宝元, 何权瀛. 重视睡眠呼吸暂停相关性高血压的诊断和防治. 中华医学杂志, 2009, 89(26): 1801-1803.
5. 梁瑞玲, 任寿安. 阻塞性睡眠呼吸暂停合并高血压发病机制研究进展. 中华高血压杂志, 2018, 26(3): 288-291.
6. 盛红宇, 姚晓光, 木拉力别克, 等. 短期持续正压通气治疗对不同性别 OSAHS 合并高血压患者降压疗效的比较. 中华全科医学, 2016, 14(1): 9-11.
7. 徐小华, 韩志强, 田明庆, 等. 高血压合并阻塞性睡眠呼吸暂停低通气综合征患者持续气道正压通气治疗前后血压与血管紧张素水平的研究. 浙江中医药大学学报, 2014, 38(5): 595-597.
8. 李黎, 王怀振, 杨晓红, 等. 持续气道正压通气在 OSAHS 合并高血压患者中的疗效评价. 中国医药科学, 2014, 4(21): 9-11.
9. Kanagy NL, Walker BR, Nelin LD. Role of endothelin in intermittent hypoxia-induced hypertension. Hypertension, 2001, 37(2 Pt 2): 511-515.
10. Fletcher EC. Physiological consequences of intermittent hypoxia: systemic blood pressure. J Appl Physiol, 2001, 90(4): 1600-1605.
11. 罗荧荃, 黄国庆, 杨宇. 慢性间歇低氧诱发大鼠高血压模型的建立. 中国新药杂志, 2006, 15(22): 1930-1933.
12. 吴晓丹, 黄建浩, 孔德红, 等. 慢性间歇低氧大鼠模型的建立和超声心动图评价. 复旦学报(医学版), 2011, 38(6): 481-484.
13. 蒋丽君, 刘建红, 宋玮, 等. 慢性间歇低氧并高血压 SD 大鼠模型的建立. 中国临床新医学, 2015, 8(11): 1013-1015.
14. Chalmers AH. Simple, sensitive measurement of carbon monoxide in plasma. Clin Chem, 1997, 37(8): 1442-1445.
15. 申洪. 免疫组织化学染色定量方法研究. 中国组织化学与细胞化学杂志, 1995, 4(1): 89-91.
16. Ndismag JF, Wang R. Age-related alterations in soluble guanylyl cyclase and cGMP pathway in spontaneously hypertensive rats. J Hypertens, 2003, 21(6): 1117-1124.
17. 李瑞珍. Hemin 对妊娠期高血压疾病大鼠 HO-1 的表达、血压及尿蛋白的影响[D]. 湖南: 中南大学湘雅三医院, 2014, 1-2.
18. 李玉明, 郑新程, 刘俊昌, 等. LPS 对培养的大鼠主动脉平滑肌细胞 HO-1 表达的影响. 中国病理生理杂志, 2000, 16(10): 1012-1013.

Chinese Journal of Respiratory and Critical Care Medicine

Study of hemin in intermittent hypoxic rats

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