Abstract:
:Bile duct obstruction is associated with hepatic accumulation of leukocytes and liver injury. Emerging data suggest that platelets may play an important role in tissue damage and inflammation. Herein, we characterized the platelet response in cholestatic liver injury and evaluated the role of Rho-kinase signaling. For this purpose, C57BL/6 mice were treated with the Rho-kinase inhibitor Y-27632 (10 mg/kg) and vehicle before undergoing bile duct ligation (BDL) for 12 h. Platelet rolling and adhesion, formation of platelet aggregates as well as microvascular perfusion in the liver were analyzed using intravital fluorescence microscopy. Liver damage was monitored by measuring serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Administration of Y-27632 reduced the BDL-associated increase of ALT and AST by 95% and 89%, respectively. The inhibition of Rho-kinase also reduced cholestasis-induced platelet rolling and adhesion by more than 46% and 73% in postsinusoidal venules and platelet adhesion in sinusoids by 60%. In addition, Y-27632 decreased platelet aggregation in hepatic sinusoids and postsinusoidal venules by 69% and 81%. BDL caused a significant reduction of hepatic microvascular perfusion. Importantly, pretreatment with Y-27632 restored sinusoidal perfusion in cholestatic animals. Our findings demonstrate that Rho-kinase regulates multiple aspects of platelet interaction in the microcirculation of cholestatic animals. Moreover, inhibition of Rho-kinase signaling not only attenuates platelet responses but also maintains microvascular perfusion and protects against hepatocellular injury in cholestasis. Thus, targeting Rho-kinase signaling may be an effective way to protect against platelet-mediated liver injury in obstructive jaundice.
journal_name
Microvasc Resjournal_title
Microvascular researchauthors
Laschke MW,Dold S,Menger MD,Jeppsson B,Thorlacius Hdoi
10.1016/j.mvr.2009.04.003subject
Has Abstractpub_date
2009-06-01 00:00:00pages
95-9issue
1eissn
0026-2862issn
1095-9319pii
S0026-2862(09)00134-4journal_volume
78pub_type
杂志文章abstract::We investigated the role of nitric oxide synthase (NOS) on regional cutaneous vascular function at rest (thermoneutral conditions) and during the vasodilator response to increased local skin temperature (Tloc). Dorsal forearm and lateral leg sites were instrumented with microdialysis fibers, local heaters, and laser-D...
journal_title:Microvascular research
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doi:
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abstract::Endometriosis, the presence of endometrium-like tissue outside of the uterine cavity, is a common disease among women of reproductive age. Typical symptoms include abdominal pain and painful menstruation. In addition, endometriosis is associated with reduced fertility. Current treatment modalities, the surgical remova...
journal_title:Microvascular research
pub_type: 杂志文章,评审
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journal_title:Microvascular research
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journal_title:Microvascular research
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journal_title:Microvascular research
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journal_title:Microvascular research
pub_type: 杂志文章
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2017.04.003
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journal_title:Microvascular research
pub_type: 杂志文章
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更新日期:2019-05-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1997.2045
更新日期:1998-01-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1995.1064
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journal_title:Microvascular research
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2014.02.001
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journal_title:Microvascular research
pub_type: 杂志文章,评审
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journal_title:Microvascular research
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journal_title:Microvascular research
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journal_title:Microvascular research
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journal_title:Microvascular research
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journal_title:Microvascular research
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