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INFLAMMATION/IMMUNITY/MEDIATORS

Potential of 3,4-dihydroxy-phenyl lactic acid for ameliorating ischemia-reperfusion-induced microvascular disturbance in rat mesentery

¹Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China; ²Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan; ³Department of Internal Medicine, National Defense Medical College, Saitama, Japan; ⁴Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China

Submitted 8 April 2008 ; accepted in final form 11 November 2008

This study intended to examine the effect of 3,4-dihydroxy-phenyl lactic acid (DLA), a major ingredient of Salvia miltiorrhiza, on ischemia-reperfusion (I/R)-induced rat mesenteric microcirculatory injury. DLA (5 mg·kg^–1·h^–1), superoxide dismutase (SOD, 12,000 U·kg^–1·h^–1), 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, FITC-albumin leakage, dihydrorhodamine 123 fluorescence, and mast cell degranulation were determined using an intravital microscope. 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 pretreatment with DLA significantly reduced peroxide production in and leukocyte adhesion to venular wall, albumin leakage, and mast cell degranulation induced by I/R. The DLA posttreatment exerted an ameliorating effect on I/R-induced disorders as well, characterized by inhibiting further increase in peroxide production in venular wall and albumin leakage 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 either SOD or CAT were 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.

leukocyte adhesion; mast cell degranulation; oxidative stress; Salvia miltiorrhiza