Frontiers in Physiology (Oct 2019)
YangXue QingNao Wan, a Compound Chinese Medicine, Attenuates Cerebrovascular Hyperpermeability and Neuron Injury in Spontaneously Hypertensive Rat: Effect and Mechanism
- 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
Affiliations
- Ying-Qian Jiao
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Ying-Qian Jiao
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Ying-Qian Jiao
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Ying-Qian Jiao
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Ying-Qian Jiao
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Ying-Qian Jiao
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, China
- Ping Huang
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Ping Huang
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Ping Huang
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Ping Huang
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Ping Huang
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, China
- Li Yan
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Li Yan
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Li Yan
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Li Yan
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Li Yan
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, China
- Kai Sun
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Kai Sun
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Kai Sun
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Kai Sun
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Kai Sun
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, China
- Chun-Shui Pan
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Chun-Shui Pan
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Chun-Shui Pan
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Chun-Shui Pan
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Chun-Shui Pan
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, China
- Quan Li
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Quan Li
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Quan Li
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Quan Li
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Quan Li
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, China
- Jing-Yu Fan
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Jing-Yu Fan
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, China
- Zhi-Zhong Ma
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Zhi-Zhong Ma
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Zhi-Zhong Ma
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Zhi-Zhong Ma
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Zhi-Zhong Ma
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, China
- Jing-Yan Han
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Jing-Yan Han
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Jing-Yan Han
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Jing-Yan Han
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Jing-Yan Han
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Jing-Yan Han
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Beijing, China
- DOI
- https://doi.org/10.3389/fphys.2019.01246
- Journal volume & issue
-
Vol. 10
Abstract
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.
Keywords
