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, 儲德節, 洪燕, 等. 阻塞性睡眠呼吸暫停低通氣綜合征與高血壓的相關性及危險因素分析. 中國臨床醫學, 2015, 11(6): 750-753.
2.	劉旺, 彭敏, 劉土軒, 等. 不同程度的 OSAHS 合并高血壓患者在不同時間段的血壓水平對比觀察. 中國實用醫藥, 2017, 12(30): 40-41.
3.	王維維, 英俊岐, 高春燕, 等. 阻塞性睡眠呼吸暫停低通氣綜合征與老年高血壓的相關性. 中國地方病防治雜志, 2017, 32(7): 730-731.
4.	陳寶元, 何權瀛. 重視睡眠呼吸暫停相關性高血壓的診斷和防治. 中華醫學雜志, 2009, 89(26): 1801-1803.
5.	梁瑞玲, 任壽安. 阻塞性睡眠呼吸暫停合并高血壓發病機制研究進展. 中華高血壓雜志, 2018, 26(3): 288-291.
6.	盛紅宇, 姚曉光, 木拉力別克, 等. 短期持續正壓通氣治療對不同性別 OSAHS 合并高血壓患者降壓療效的比較. 中華全科醫學, 2016, 14(1): 9-11.
7.	徐小華, 韓志強, 田明慶, 等. 高血壓合并阻塞性睡眠呼吸暫停低通氣綜合征患者持續氣道正壓通氣治療前后血壓與血管緊張素水平的研究. 浙江中醫藥大學學報, 2014, 38(5): 595-597.
8.	李黎, 王懷振, 楊曉紅, 等. 持續氣道正壓通氣在 OSAHS 合并高血壓患者中的療效評價. 中國醫藥科學, 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.	羅熒荃, 黃國慶, 楊宇. 慢性間歇低氧誘發大鼠高血壓模型的建立. 中國新藥雜志, 2006, 15(22): 1930-1933.
12.	吳曉丹, 黃建浩, 孔德紅, 等. 慢性間歇低氧大鼠模型的建立和超聲心動圖評價. 復旦學報(醫學版), 2011, 38(6): 481-484.
13.	蔣麗君, 劉建紅, 宋瑋, 等. 慢性間歇低氧并高血壓 SD 大鼠模型的建立. 中國臨床新醫學, 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. 免疫組織化學染色定量方法研究. 中國組織化學與細胞化學雜志, 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 對妊娠期高血壓疾病大鼠 HO-1 的表達、血壓及尿蛋白的影響[D]. 湖南: 中南大學湘雅三醫院, 2014, 1-2.
18.	李玉明, 鄭新程, 劉俊昌, 等. LPS 對培養的大鼠主動脈平滑肌細胞 HO-1 表達的影響. 中國病理生理雜志, 2000, 16(10): 1012-1013.

1. 朱小川, 儲德節, 洪燕, 等. 阻塞性睡眠呼吸暫停低通氣綜合征與高血壓的相關性及危險因素分析. 中國臨床醫學, 2015, 11(6): 750-753.
2. 劉旺, 彭敏, 劉土軒, 等. 不同程度的 OSAHS 合并高血壓患者在不同時間段的血壓水平對比觀察. 中國實用醫藥, 2017, 12(30): 40-41.
3. 王維維, 英俊岐, 高春燕, 等. 阻塞性睡眠呼吸暫停低通氣綜合征與老年高血壓的相關性. 中國地方病防治雜志, 2017, 32(7): 730-731.
4. 陳寶元, 何權瀛. 重視睡眠呼吸暫停相關性高血壓的診斷和防治. 中華醫學雜志, 2009, 89(26): 1801-1803.
5. 梁瑞玲, 任壽安. 阻塞性睡眠呼吸暫停合并高血壓發病機制研究進展. 中華高血壓雜志, 2018, 26(3): 288-291.
6. 盛紅宇, 姚曉光, 木拉力別克, 等. 短期持續正壓通氣治療對不同性別 OSAHS 合并高血壓患者降壓療效的比較. 中華全科醫學, 2016, 14(1): 9-11.
7. 徐小華, 韓志強, 田明慶, 等. 高血壓合并阻塞性睡眠呼吸暫停低通氣綜合征患者持續氣道正壓通氣治療前后血壓與血管緊張素水平的研究. 浙江中醫藥大學學報, 2014, 38(5): 595-597.
8. 李黎, 王懷振, 楊曉紅, 等. 持續氣道正壓通氣在 OSAHS 合并高血壓患者中的療效評價. 中國醫藥科學, 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. 羅熒荃, 黃國慶, 楊宇. 慢性間歇低氧誘發大鼠高血壓模型的建立. 中國新藥雜志, 2006, 15(22): 1930-1933.
12. 吳曉丹, 黃建浩, 孔德紅, 等. 慢性間歇低氧大鼠模型的建立和超聲心動圖評價. 復旦學報(醫學版), 2011, 38(6): 481-484.
13. 蔣麗君, 劉建紅, 宋瑋, 等. 慢性間歇低氧并高血壓 SD 大鼠模型的建立. 中國臨床新醫學, 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. 免疫組織化學染色定量方法研究. 中國組織化學與細胞化學雜志, 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 對妊娠期高血壓疾病大鼠 HO-1 的表達、血壓及尿蛋白的影響[D]. 湖南: 中南大學湘雅三醫院, 2014, 1-2.
18. 李玉明, 鄭新程, 劉俊昌, 等. LPS 對培養的大鼠主動脈平滑肌細胞 HO-1 表達的影響. 中國病理生理雜志, 2000, 16(10): 1012-1013.

Chinese Journal of Respiratory and Critical Care Medicine

Study of hemin in intermittent hypoxic rats

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