Frontiers in Pharmacology (Jan 2022)
QiShenYiQi Inhibits Tissue Plasminogen Activator–Induced Brain Edema and Hemorrhage after Ischemic Stroke in Mice
- Yang Ye,
- Yang Ye,
- Yang Ye,
- Yang Ye,
- Yang Ye,
- Yang Ye,
- Quan Li,
- Quan Li,
- Quan Li,
- Quan Li,
- Quan Li,
- Chun-Shui Pan,
- Chun-Shui Pan,
- Chun-Shui Pan,
- Chun-Shui Pan,
- Chun-Shui Pan,
- Li Yan,
- Li Yan,
- Li Yan,
- Li Yan,
- Li Yan,
- Kai Sun,
- Kai Sun,
- Kai Sun,
- Kai Sun,
- Kai Sun,
- Xiao-Yi Wang,
- Xiao-Yi Wang,
- Xiao-Yi Wang,
- Xiao-Yi Wang,
- Xiao-Yi Wang,
- Xiao-Yi Wang,
- Shu-Qi Yao,
- Shu-Qi Yao,
- Shu-Qi Yao,
- Shu-Qi Yao,
- Shu-Qi Yao,
- Shu-Qi Yao,
- Jing-Yu Fan,
- Jing-Yu Fan,
- Jing-Yu Fan,
- Jing-Yu Fan,
- Jing-Yu Fan,
- Jing-Yan Han,
- Jing-Yan Han,
- Jing-Yan Han,
- Jing-Yan Han,
- Jing-Yan Han,
- Jing-Yan Han
Affiliations
- Yang Ye
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Yang Ye
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Yang Ye
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Yang Ye
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Yang Ye
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Yang Ye
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Quan Li
- Tasly Microcirculation Research Center, Peking University Health Science Center, 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
- Key Laboratory of Stasis and Phlegm, 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, Tianjin, China
- Chun-Shui Pan
- Tasly Microcirculation Research Center, Peking University Health Science Center, 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
- Key Laboratory of Stasis and Phlegm, 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, Tianjin, China
- Li Yan
- Tasly Microcirculation Research Center, Peking University Health Science Center, 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
- Key Laboratory of Stasis and Phlegm, 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, Tianjin, China
- Kai Sun
- Tasly Microcirculation Research Center, Peking University Health Science Center, 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
- Key Laboratory of Stasis and Phlegm, 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, Tianjin, China
- Xiao-Yi Wang
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Xiao-Yi Wang
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Xiao-Yi Wang
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Xiao-Yi Wang
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Xiao-Yi Wang
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Xiao-Yi Wang
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Shu-Qi Yao
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Shu-Qi Yao
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Shu-Qi Yao
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Shu-Qi Yao
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Shu-Qi Yao
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Shu-Qi Yao
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Jing-Yu Fan
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Jing-Yu Fan
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Jing-Yu Fan
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Jing-Yu Fan
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Jing-Yu Fan
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Jing-Yan Han
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Jing-Yan Han
- Tasly Microcirculation Research Center, Peking University Health Science Center, 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
- Key Laboratory of Stasis and Phlegm, 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, Tianjin, China
- DOI
- https://doi.org/10.3389/fphar.2021.759027
- Journal volume & issue
-
Vol. 12
Abstract
Background: Thrombolysis with tissue plasminogen activator (tPA) remains the only approved drug therapy for acute ischemic stroke. However, delayed tPA treatment is associated with an increased risk of brain hemorrhage. In this study, we assessed whether QiShenYiQi (QSYQ), a compound Chinese medicine, can attenuate tPA-induced brain edema and hemorrhage in an experimental stroke model.Methods: Male mice were subjected to ferric chloride-induced carotid artery thrombosis followed by mechanical detachment of thrombi. Then mice were treated with QSYQ at 2.5 h followed by administration of tPA (10 mg/kg) at 4.5 h. Hemorrhage, infarct size, neurological score, cerebral blood flow, Evans blue extravasation, FITC-labeled albumin leakage, tight and adherens junction proteins expression, basement membrane proteins expression, matrix metalloproteinases (MMPs) expression, leukocyte adhesion, and leukocyte infiltration were assessed 24 h after tPA administration.Results: Compared with tPA alone treatments, the combination therapy of QSYQ and tPA significantly reduced hemorrhage, infarction, brain edema, Evans blue extravasation, albumin leakage, leukocyte adhesion, MMP-9 expression, and leukocyte infiltration at 28.5 h after stroke. The combination also significantly improved the survival rate, cerebral blood flow, tight and adherens junction proteins (occludin, claudin-5, junctional adhesion molecule-1, zonula occludens-1, VE-cadherin, α-catenin, β-catenin) expression, and basement membrane proteins (collagen IV, laminin) expression. Addition of QSYQ protected the downregulated ATP 5D and upregulated p-Src and Caveolin-1 after tPA treatment.Conclusion: Our results show that QSYQ inhibits tPA-induced brain edema and hemorrhage by protecting the blood-brain barrier integrity, which was partly attributable to restoration of energy metabolism, protection of inflammation and Src/Caveolin signaling activation. The present study supports QSYQ as an effective adjunctive therapy to increase the safety of delayed tPA thrombolysis for ischemic stroke.
Keywords
