YangXue QingNao Wan, a Compound Chinese Medicine, Attenuates Cerebrovascular Hyperpermeability and Neuron Injury in Spontaneously Hypertensive Rat: Effect and Mechanism
ObjectiveThe purpose of the study was to explore the effect of YangXue QingNao Wan (YXQNW), a compound Chinese medicine, on cerebrovascular hyperpermeability, neuronal injury, and related mechanisms in spontaneously hypertensive rat (SHR).MethodsFourteen-week-old male SHR were used, with Wistar Kyot...
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Frontiers Media S.A.
2019-10-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2019.01246/full |
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| author | Ying-Qian Jiao Ying-Qian Jiao Ying-Qian Jiao Ying-Qian Jiao Ying-Qian Jiao Ying-Qian Jiao Ping Huang Ping Huang Ping Huang Ping Huang Ping Huang Li Yan Li Yan Li Yan Li Yan Li Yan Kai Sun Kai Sun Kai Sun Kai Sun Kai Sun Chun-Shui Pan Chun-Shui Pan Chun-Shui Pan Chun-Shui Pan Chun-Shui Pan Quan Li Quan Li Quan Li Quan Li Quan Li Jing-Yu Fan Jing-Yu Fan Zhi-Zhong Ma Zhi-Zhong Ma Zhi-Zhong Ma Zhi-Zhong Ma Zhi-Zhong Ma Jing-Yan Han Jing-Yan Han Jing-Yan Han Jing-Yan Han Jing-Yan Han Jing-Yan Han |
| author_facet | Ying-Qian Jiao Ying-Qian Jiao Ying-Qian Jiao Ying-Qian Jiao Ying-Qian Jiao Ying-Qian Jiao Ping Huang Ping Huang Ping Huang Ping Huang Ping Huang Li Yan Li Yan Li Yan Li Yan Li Yan Kai Sun Kai Sun Kai Sun Kai Sun Kai Sun Chun-Shui Pan Chun-Shui Pan Chun-Shui Pan Chun-Shui Pan Chun-Shui Pan Quan Li Quan Li Quan Li Quan Li Quan Li Jing-Yu Fan Jing-Yu Fan Zhi-Zhong Ma Zhi-Zhong Ma Zhi-Zhong Ma Zhi-Zhong Ma Zhi-Zhong Ma Jing-Yan Han Jing-Yan Han Jing-Yan Han Jing-Yan Han Jing-Yan Han Jing-Yan Han |
| author_sort | Ying-Qian Jiao |
| collection | DOAJ |
| description | ObjectiveThe purpose of the study was to explore the effect of YangXue QingNao Wan (YXQNW), a compound Chinese medicine, on cerebrovascular hyperpermeability, neuronal injury, and related mechanisms in spontaneously hypertensive rat (SHR).MethodsFourteen-week-old male SHR were used, with Wistar Kyoto (WKY) rats as control. YXQNW (0.5 g/kg/day), enalapril (EN, 8 mg/kg/day), and nifedipine (NF, 7.1 mg/kg/day) were administrated orally for 4 weeks. To assess the effects of the YXQNW on blood pressure, the systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) were measured. After administering the drugs for 4 weeks, the cerebral blood flow (CBF), albumin leakage from microvessels in middle cerebral artery (MCA)-dominated area, and the number and morphology of microvessels were assessed in the hippocampus area and cortex. Neuronal damage and apoptosis were assessed by Nissl staining and TUNEL staining. To assess the mechanisms of cerebrovascular hyperpermeability, we performed immunofluorescence and Western blot to assess the expression and integrity of cerebral microvascular tight junction (TJ) and caveolin-1 (Cav-1) in cortex. Energy metabolism and Src-MLC-MLCK pathway in cortex were assessed then for elucidating the underlying mechanism of the observed effect of YXQNW.ResultsSpontaneously hypertensive rat exhibited higher blood pressure, Evans blue (EB) extravasation, albumin leakage, increased brain water content, decreased CBF, perivascular edema, and neuronal apoptosis in the hippocampus and cortex, all of which were attenuated by YXQNW treatment. YXQNW inhibited the downregulation of TJ proteins, mitochondrial Complex I, Complex II, and Complex V, and upregulation of caveolin-1, inhibiting Src/MLCK/MLC signaling in SHR. YXQNW combined with EN + NF revealed a better effect for some outcomes compared with either YXQNW or EN + NF alone.ConclusionThe overall result shows the potential of YXQNW to attenuate blood–brain barrier (BBB) breakdown in SHR, which involves regulation of energy metabolism and Src/MLCK/MLC signaling. This result provides evidence supporting the application of YXQNW as an adjuvant management for hypertensive patients to prevent hypertensive encephalopathy. |
| first_indexed | 2024-12-10T05:17:43Z |
| format | Article |
| id | doaj.art-50eca74e303540eaa65d5141da8bfc77 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-10T05:17:43Z |
| publishDate | 2019-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-50eca74e303540eaa65d5141da8bfc772022-12-22T02:00:54ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2019-10-011010.3389/fphys.2019.01246474913YangXue QingNao Wan, a Compound Chinese Medicine, Attenuates Cerebrovascular Hyperpermeability and Neuron Injury in Spontaneously Hypertensive Rat: Effect and MechanismYing-Qian Jiao0Ying-Qian Jiao1Ying-Qian Jiao2Ying-Qian Jiao3Ying-Qian Jiao4Ying-Qian Jiao5Ping Huang6Ping Huang7Ping Huang8Ping Huang9Ping Huang10Li Yan11Li Yan12Li Yan13Li Yan14Li Yan15Kai Sun16Kai Sun17Kai Sun18Kai Sun19Kai Sun20Chun-Shui Pan21Chun-Shui Pan22Chun-Shui Pan23Chun-Shui Pan24Chun-Shui Pan25Quan Li26Quan Li27Quan Li28Quan Li29Quan Li30Jing-Yu Fan31Jing-Yu Fan32Zhi-Zhong Ma33Zhi-Zhong Ma34Zhi-Zhong Ma35Zhi-Zhong Ma36Zhi-Zhong Ma37Jing-Yan Han38Jing-Yan Han39Jing-Yan Han40Jing-Yan Han41Jing-Yan Han42Jing-Yan Han43Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, ChinaTasly Microcirculation Research Center, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, ChinaAcademy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, ChinaState Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, ChinaTasly Microcirculation Research Center, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, ChinaAcademy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, ChinaState Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, ChinaTasly Microcirculation Research Center, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, ChinaAcademy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, ChinaState Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, ChinaTasly Microcirculation Research Center, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, ChinaAcademy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, ChinaState Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, ChinaTasly Microcirculation Research Center, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, ChinaAcademy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, ChinaState Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, ChinaTasly Microcirculation Research Center, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, ChinaAcademy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, ChinaState Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, ChinaTasly Microcirculation Research Center, Peking University Health Science Center, Beijing, ChinaState Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, ChinaTasly Microcirculation Research Center, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, ChinaAcademy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, ChinaState Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, ChinaTasly Microcirculation Research Center, Peking University Health Science Center, Beijing, ChinaTasly Microcirculation Research Center, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, ChinaAcademy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, ChinaState Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, ChinaObjectiveThe purpose of the study was to explore the effect of YangXue QingNao Wan (YXQNW), a compound Chinese medicine, on cerebrovascular hyperpermeability, neuronal injury, and related mechanisms in spontaneously hypertensive rat (SHR).MethodsFourteen-week-old male SHR were used, with Wistar Kyoto (WKY) rats as control. YXQNW (0.5 g/kg/day), enalapril (EN, 8 mg/kg/day), and nifedipine (NF, 7.1 mg/kg/day) were administrated orally for 4 weeks. To assess the effects of the YXQNW on blood pressure, the systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) were measured. After administering the drugs for 4 weeks, the cerebral blood flow (CBF), albumin leakage from microvessels in middle cerebral artery (MCA)-dominated area, and the number and morphology of microvessels were assessed in the hippocampus area and cortex. Neuronal damage and apoptosis were assessed by Nissl staining and TUNEL staining. To assess the mechanisms of cerebrovascular hyperpermeability, we performed immunofluorescence and Western blot to assess the expression and integrity of cerebral microvascular tight junction (TJ) and caveolin-1 (Cav-1) in cortex. Energy metabolism and Src-MLC-MLCK pathway in cortex were assessed then for elucidating the underlying mechanism of the observed effect of YXQNW.ResultsSpontaneously hypertensive rat exhibited higher blood pressure, Evans blue (EB) extravasation, albumin leakage, increased brain water content, decreased CBF, perivascular edema, and neuronal apoptosis in the hippocampus and cortex, all of which were attenuated by YXQNW treatment. YXQNW inhibited the downregulation of TJ proteins, mitochondrial Complex I, Complex II, and Complex V, and upregulation of caveolin-1, inhibiting Src/MLCK/MLC signaling in SHR. YXQNW combined with EN + NF revealed a better effect for some outcomes compared with either YXQNW or EN + NF alone.ConclusionThe overall result shows the potential of YXQNW to attenuate blood–brain barrier (BBB) breakdown in SHR, which involves regulation of energy metabolism and Src/MLCK/MLC signaling. This result provides evidence supporting the application of YXQNW as an adjuvant management for hypertensive patients to prevent hypertensive encephalopathy.https://www.frontiersin.org/article/10.3389/fphys.2019.01246/fullhypertensiontight junctioncaveolin-1blood–brain barrierATPmicrovessel |
| spellingShingle | Ying-Qian Jiao Ying-Qian Jiao Ying-Qian Jiao Ying-Qian Jiao Ying-Qian Jiao Ying-Qian Jiao Ping Huang Ping Huang Ping Huang Ping Huang Ping Huang Li Yan Li Yan Li Yan Li Yan Li Yan Kai Sun Kai Sun Kai Sun Kai Sun Kai Sun Chun-Shui Pan Chun-Shui Pan Chun-Shui Pan Chun-Shui Pan Chun-Shui Pan Quan Li Quan Li Quan Li Quan Li Quan Li Jing-Yu Fan Jing-Yu Fan Zhi-Zhong Ma Zhi-Zhong Ma Zhi-Zhong Ma Zhi-Zhong Ma Zhi-Zhong Ma Jing-Yan Han Jing-Yan Han Jing-Yan Han Jing-Yan Han Jing-Yan Han Jing-Yan Han YangXue QingNao Wan, a Compound Chinese Medicine, Attenuates Cerebrovascular Hyperpermeability and Neuron Injury in Spontaneously Hypertensive Rat: Effect and Mechanism Frontiers in Physiology hypertension tight junction caveolin-1 blood–brain barrier ATP microvessel |
| title | YangXue QingNao Wan, a Compound Chinese Medicine, Attenuates Cerebrovascular Hyperpermeability and Neuron Injury in Spontaneously Hypertensive Rat: Effect and Mechanism |
| title_full | YangXue QingNao Wan, a Compound Chinese Medicine, Attenuates Cerebrovascular Hyperpermeability and Neuron Injury in Spontaneously Hypertensive Rat: Effect and Mechanism |
| title_fullStr | YangXue QingNao Wan, a Compound Chinese Medicine, Attenuates Cerebrovascular Hyperpermeability and Neuron Injury in Spontaneously Hypertensive Rat: Effect and Mechanism |
| title_full_unstemmed | YangXue QingNao Wan, a Compound Chinese Medicine, Attenuates Cerebrovascular Hyperpermeability and Neuron Injury in Spontaneously Hypertensive Rat: Effect and Mechanism |
| title_short | YangXue QingNao Wan, a Compound Chinese Medicine, Attenuates Cerebrovascular Hyperpermeability and Neuron Injury in Spontaneously Hypertensive Rat: Effect and Mechanism |
| title_sort | yangxue qingnao wan a compound chinese medicine attenuates cerebrovascular hyperpermeability and neuron injury in spontaneously hypertensive rat effect and mechanism |
| topic | hypertension tight junction caveolin-1 blood–brain barrier ATP microvessel |
| url | https://www.frontiersin.org/article/10.3389/fphys.2019.01246/full |
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