Danshen protects liver grafts from ischemia/reperfusion injury in experimental liver transplantation in rats.
Reperfusion injury remains one of the major problems in transplantation. Free radicals and disturbance of microcirculation are the supposed main contributors. Recent evidence shows that Danshen, a traditional Chinese drug used in vascular diseases, can scavenge radicals and improve microcirculation. This study investigates its effect on liver transplantation (LTx). Before organ recovery, female Sprague-Dawley rats (210-240 g) received intravenous Danshen or the same volume of Ringer solution as control. LTx was performed after 1 h of cold storage. Microperfusion, leukocyte-endothelium interaction and latex-bead phagocytosis were evaluated with in vivo microscopy. Survival, transaminases and histology were assessed. Immunohistology was used for TNF-alpha levels. anova and Fisher's exact test were employed for statistical analyses as appropriate. Survival increased from 60% in controls to 100% (P < 0.05). AST and LDH decreased from 3969 +/- 1255 U/l and 15444 +/- 5148 U/l in controls to 1236 +/- 410 U/l and 5039 +/- 1594 U/l, respectively (P < 0.05). In vivo microscopy revealed decreased leukocyte-adherence and increased blood flow velocity in sinusoidal zones after administration of Danshen (P < 0.05), while latex-bead phagocytosis was found in 60% of controls (P < 0.05). The TNF-alpha index decreased from 2.08 +/- 0.09 in controls to 1.09 +/- 0.09 (P < 0.05). This study clearly demonstrates hepatoprotective effects after experimental LTx, which can be explained via anti-oxidative effects, improved microcirculation and decreased Kupffer cell activation.
Liang
Rui
R
Department of General Surgery, Ruprecht-Karls-University, Heidelberg, Germany.
Bruns
Helge
H
Kincius
Marius
M
Lin
Tao
T
Ludwig
Jochen
J
Dei-Anane
Genevieve
G
Guan
Xiaohai
X
Gebhard
Martha-Maria
MM
Büchler
Markus W
MW
Schemmer
Peter
P
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D007728:Kupffer Cells / Q000187:drug effects / Q000276:immunology; D007962:Leukocytes / Q000502:physiology; D008099:Liver / Q000098:blood supply* / Q000648:ultrastructure; D016031:Liver Transplantation; D008833:Microcirculation / Q000187:drug effects; D008863:Microspheres; D018384:Oxidative Stress / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D008517:Phytotherapy; D011183:Postoperative Complications / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D027561:Salvia miltiorrhiza; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D004365:Drugs, Chinese Herbal; D016166:Free Radical Scavengers; D014409:Tumor Necrosis Factor-alpha; C028972:dan-shen root extract