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1 Peking University Health Science Center
2 National Defense Medical College
* To whom correspondence should be addressed. E-mail: hanjingyan{at}bjmu.edu.cn.
This study intended to examine the effect of 3, 4-dihydroxy-phenyl lactic acid (DLA, a major ingredient of Salvia miltiorrhiza (SM.) on ischemia/reperfusion (I/R)-induced rat mesenteric microcirculatory injury through an intravital microscope. DLA (5 mg/kg/hr), superoxide dismutase (SOD 12000 units/kg/hr) or catalase (CAT, 20 mg/kg) was continuously infused either starting from 10 min before the ischemia or 10 min after the initiation of reperfusion. The venule diameter, number of adherent leukocytes, dihydrorhodamine 123 (DHR) fluorescence and mast cell degranulation were determined. The production of hydrogen peroxide (H2O2) and the expression of adhesion molecules CD11b/CD18 in neutrophils were evaluated by in vitro experiments. The results showed that pre-treatment with DLA reduced significantly peroxide production in, and leukocyte adhesion to venular wall, and mast cell degranulation induced by I/R. The DLA post-treatment exerted ameliorating effect on I/R induced disorders as well, characterized by inhibiting further increase in peroxide production in venular wall and diminishing the number of leukocytes that had adhered to the venular wall. In vitro experiments revealed that treatment with DLA significantly attenuated TNF-
plus fMLP evoked production of H2O2 and the H2O2 elicited expression of CD11b/CD18 on neutrophils. SOD and CAT manifested similarly but with the exception that SOD or CAT was unable to retrieve the adherent leukocytes if administrated after initiation of reperfusion and to depress the H2O2 induced expression of CD11b/CD18 on neutrophils. It is concluded that DLA protects from and ameliorates the I/R induced microcirculatory disturbance by interfering with both peroxide production and adhesion molecule expression.
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