[Effect of paeoniflorin on hepatic immunopathogenesis in mice with Schistosoma japonicum infection].
OBJECTIVE
To investigate the mechanism of paeoniflorin in preventing hepatic granuloma formation and fibrosis in mice infected with Schistosoma japonicum.


METHODS
Model of hepatic granuloma and fibrosis was established by infecting mice with S. japonicum cercariae. The infected mice were randomly divided into 4 groups: group A as model (infected control) group (15 mice), and paeoniflorin being given before, simultaneously and after praziquantel treatment as groups B, C and D. Each of the groups B, C and D was subdivided into 3 subgroups (15 mice each): low dose (paeoniflorin 2 ml, 30 mg/(kg x d) x 30 d), high dose(paeoniflorin 2 ml, 120 mg/(kg x d) x 30 d) and control (2 ml, 0.5% sodium carboxymethylcellulose x 30 d). In group B, paeoniflorin or sodium carboxymethylcellulose was orally administrated on 12 d after infection. In groups C and D, paeoniflorin or sodium carboxymethylcellulose was administrated on 42 d or 72 d after infection. Each of group B, C and D was orally given praziquantel 2 ml (500 mg/(kg x d) x 2 d) on 42 d after infection. On the 102nd day after infection, all animals were sacrificed by cervical dislocation. Serum hyaluronic acid (HA) was detected by radioimmunoassay; area of egg granuloma and degree of hepatic fibrosis were observed via HE and Masson stainings; the expression of transforming growth factor beta1 (TGF-beta1), alpha smooth muscle actin (alpha-SMA and collagen I (Col I) protein were measured by immunohistochemical method.


RESULTS
In group B, the level of HA (0.719 +/- 0.239 microg/ml, 0.721 +/- 0.182 microg/ml) in low or high dose subgroups was significantly lower (F = 9.429, P < 0.01) than the control subgroup (1.049 +/- 0.286 microg/ml); the area of granuloma (0.066 +/- 0.005 mm2, 0.064 +/- 0.004 mm2) or the degree of hepatic fibrosis (2.067 +/- 0.458, 1.967 +/- 0.399) in low or high dose subgroups was significantly greater (F = 862.540, F = 29.738, P < 0.01) than the control (0.141 +/- 0.008 mm2, 3.467 +/- 0.834); the expression of alpha-SMA positive cells (2.933 +/- 0.594, 3.000 +/- 0.535) in low or high dose subgroups was significantly lower (F = 12.323, P < 0.01, P < 0.01) than its control (4.800 +/- 1.859); the expression of TGF-beta1 (0.256 +/- 0.057, 0.274 +/- 0.054) in low or high dose subgroups was significantly lower (F = 148.990, P < 0.01) than its control (0.552 +/- 0.047); the content of Col I (0.334 +/- 0.041, 0.339 +/- 0.042) in low or high dose subgroups was significantly lower (F = 180.881, P < 0.01) than its control (0.601 +/- 0.049). In groups C & D, no significant difference was found between the low or high dose subgroups or between the subgroups and their corresponding controls.


CONCLUSIONS
Paeoniflorin can significantly reduce hepatic granuloma formation and fibrosis due to schistosome eggs, and decrease the expression of TGF-beta1, alpha-SMA in mice when it is given before praziquantel administration, which may associate with the activation of hepatic stellate cells and the expression of TGF-beta1 in liver tissue.
Chu
De-Yong
DY
Department of Parasitology, Anhui Medical University, Ministry of Education, Hefei 230032, China.
Li
Cong-Lei
CL
Yang
Feng
F
Wu
Qiang
Q
Li
Jing
J
Ding
Xiang-Dong
XD
Luo
Qing-Li
QL
Shen
Ji-Long
JL
D000185:Actinin / Q000096:biosynthesis; D000818:Animals; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D039821:Monoterpenes; D008517:Phytotherapy; D012549:Schistosoma japonicum / Q000187:drug effects*; D012554:Schistosomiasis japonica / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D016896:Treatment Outcome; D006027:Glycosides
D000185:Actinin; D001565:Benzoates; D001952:Bridged-Ring Compounds; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D039821:Monoterpenes; D053773:Transforming Growth Factor beta1; C015423:peoniflorin; D006027:Glycosides