scholarly journals The role of Rho/Rho-kinase pathway and the neuroprotective effects of fasudil in chronic cerebral ischemia

2015 ◽  
Vol 10 (9) ◽  
pp. 1441 ◽  
Author(s):  
Yan-kun Shao ◽  
Zhong-xin Xu ◽  
Ya-yun Yan ◽  
Xiao-ming Wang ◽  
Yan Jiang ◽  
...  
2020 ◽  
Vol 4 (9) ◽  
pp. 544-551
Author(s):  
I.A. Schukin ◽  
◽  
M.S. Fidler ◽  
I.A. Koltsov ◽  
◽  
...  

Aim: to evaluate the efficacy and safety of the L-lysine escinate venotropic drug in the treatment of cephalgic, atactic and asthenic syndromes in patients with chronic cerebral ischemia, mainly caused by venous disorders. Patients and Methods: the study involved 60 patients with a diagnosis of chronic cerebral ischemia with signs of chronic venous insufficiency. All patients were randomly divided into two groups consisting of 30 people. Patients in the main group received L-lysine escinate, and the control group received Vinpocetine. The drugs were administered by intravenous drip for 10 days. A dynamic assessment was performed using a modified subjective scale of asthenia evaluation (MFI-20), 100 mm long visual analogue scale (VAS) for headache, subjective neurological impairment scale (SNIS), and Tinetti test. An ophthalmic examination with an assessment of the fundus vessels and an ultrasound duplex scanning of head vessels (veins) were also conducted. Results: it was shown that L-lysine escinate therapy showed a statistically more significant reduction in the severity of headache (according to VAS) and an improved stability measured by Tinetti test versus during Vinpocetine treatment. There were no significant differences in the level of asthenia (MFI-20), the severity of emotional disorders, and the SNIS score. Also, the number of patients with dilated fundus veins significantly decreased during treatment in the main group (p<0.05), which was not the case in the control group. According to ultrasound duplex scanning data, the venous flow velocity through the veins of Rosenthal and angular veins during L-lysine escinate therapy was significantly higher (p<0.05) than in patients receiving Vinpocetine. Conclusion: the inclusion of vasotropic drugs (in particular, the L-lysine escinate venotonic drug) in the treatment regimen of patients with chronic brain ischemia seems appropriate, especially if there are signs of venous insufficiency. KEYWORDS: systemic venous insufficiency, chronic cerebrovascular disease, venous dyscirculation, glymphatic system, L-lysine escinate, Vinpocetine. FOR CITATION: Schukin I.A., Fidler M.S., Koltsov I.A. Chronic cerebrovascular disease: the role of venous disorders and the possibility of pathogenetic correction. Russian Medical Inquiry. 2020;4(9):544–551. DOI: 10.32364/2587-6821-2020-4-9-544-551.


2011 ◽  
Vol 36 (8) ◽  
pp. 1062-1071 ◽  
Author(s):  
H Tokuyama ◽  
S Wakino ◽  
Y Hara ◽  
N Washida ◽  
K Fujimura ◽  
...  

2004 ◽  
Vol 287 (4) ◽  
pp. L673-L684 ◽  
Author(s):  
Jean-Marc Hyvelin ◽  
Clare O’Connor ◽  
Paul McLoughlin

Pulmonary arteries (PA) are resistant to the vasodilator effects of extracellular acidosis in systemic vessels; the mechanism underlying this difference between systemic and pulmonary circulations has not been elucidated. We hypothesized that RhoA/Rho-kinase-mediated Ca2+ sensitization pathway played a greater role in tension development in pulmonary than in systemic vascular smooth muscle and that this pathway was insensitive to acidosis. In arterial rings contracted with the α1-agonist phenylephrine (PE), the Rho-kinase inhibitor Y-27632 (≤3 μM) induced greater relaxation in precontracted PA rings than in aortic rings. In PA rings stimulated by PE, the activation of RhoA was greater than in aorta. Normocapnic acidosis (NA) induced a smaller relaxation in precontracted PA than in aorta. However, in the presence of nifedipine and thapsigargin, when PE-induced contraction was predominantly mediated by Rho-kinase, the relaxant effect of NA was reduced and similar in both vessel types. Furthermore, in the presence of Y-27632, NA induced a greater relaxation in both PA and aorta, which was similar in both vessels. Finally, in α-toxin-permeabilized smooth muscle, PE-induced contraction at constant Ca2+ activity was inhibited by Y-27632 and unaffected by acidosis. These results indicate that Ca2+ sensitization induced by the RhoA/Rho-kinase pathway played a greater role in agonist-induced vascular smooth muscle contraction in PA than in aorta and that tension mediated by this pathway was insensitive to acidosis. The predominant role of the RhoA/Rho-kinase pathway in the pulmonary vasculature may account for the resistance of this circulation to the vasodilator effect of acidosis observed in the systemic circulation.


2018 ◽  
Vol 45 (6) ◽  
pp. 2461-2470 ◽  
Author(s):  
Wenhua Xue ◽  
Zhirui Fan ◽  
Yuanzhe Li ◽  
Lifeng Li ◽  
Tengfei Zhang ◽  
...  

Background/Aims: The current study was designed to investigate the protective role of alkannin (ALK) on liver injury in diabetic C57BL/KsJ-db/db mice and explore its potential mechanisms. Methods: An oral glucose tolerance test (OGTT) was performed. The levels of insulin, alanine aminotransferase (ALT), aspartate aminotransaminase (AST), total cholesterol (TC) and triglyceride (TG) were determined by commercial kits. The pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α were determined by ELISA. The levels of the ROCK/NF-κB pathway were determined by Western blotting. Results: The contents of pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α were inhibited by ALK, metformin or fasudil in diabetic db/db mice. Further, Western blotting analysis showed that the expression of Rho, ROCK1, ROCK2, p-NF-κBp65, and p-IκBα was significantly reversed by ALK treatment. In human hepatic HepG2 cells, the hepatoprotective effects of ALK were further characterized. With response to palmitic acid-challenge, increased amounts of insulin, ALT, AST, TG, and TC were observed, whereas ALK pretreatment significantly inhibited their leakage in HepG2 cells without appreciable cytotoxic effects. The inflammation condition was recovered with ALK treatment as shown by changes of IL-1β, IL-6 and TNF-α. Further, Western blotting analysis also suggested that ALK improves hepatic inflammation in a Rho-kinase pathway. Conclusion: The present study successfully investigated the role of Rho-kinase signalling in diabetic liver injury. ALK exhibited hepatoprotective effects in diabetic db/db mice, and it might act through improving hepatic inflammation through the Rho-kinase pathway.


2014 ◽  
Vol 998-999 ◽  
pp. 269-274
Author(s):  
Wen Yi ◽  
Meng Qiong Shi ◽  
Guang Yao Liu ◽  
Wei Deng ◽  
Hui Lin Qin ◽  
...  

Saponins from Rhizoma Panacis Majoris (SRPM), the bioactive component in Rhizoma Panacis Majoris, were reported to possess protective effects on brain injury, but the underlying mechanisms remain poorly understood. This study was performed to investigate the protective effects and possible mechanism of SRPM on cerebral ischemia/reperfusion (CI/R) injury. Neuroprotective effects of SPRM in CI/R mice was evaluated by infarct size, biochemical values, Nuclear factor erythroid 2-related factor 2 (Nrf2) and Bcl-2 family expressions. In the study, we found that SRPM exerted beneficially protective effects on CI/R injury, mainly scavenging oxidative stress-triggered overgeneration and accumulation of reactive oxygen species, improving the Nrf2-mediated antioxidant response: role of Nrf2 and Bcl-2 family expressions, and alleviating CI/R injury and cerebral cell death.


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