title: Efficacy and mechanism of tanshinone IIA liquid nanoparticles in preventing experimental postoperative peritoneal adhesions in vivo and in vitro.
abstract: Up to 90% of patients develop adhesion following laparotomy. Upregulating fibrinolysis within the peritoneum reduces adhesions. Tanshinone IIA (Tan IIA) promotes fibrinolysis in hepatic fibrosis and the cardiovascular system and may play a role in preventing adhesions. We report preparation and characterization of liquid nanoparticles of Tan IIA for intravenous administration and investigate its feasibility in clinical practice. Tan IIA liquid nanoparticles (Tan IIA-NPs) were prepared using the emulsion/solvent evaporation method. Adhesions were induced in Sprague-Dawley rats by injuring the parietal peritoneum and cecum, followed by intravenous administration of various Tan IIA-NP dosages. The adhesion scores for each group were collected 7 days after the initial laparotomy. The activity of tissue-type plasminogen activator (tPA) was measured from the peritoneal lavage fluid. The messenger RNA and protein expression levels of plasminogen activator inhibitor-1 (PAI-1) were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. TGF-β1 and collagen I expressions were measured immunohistochemically in the ischemic tissues. The effects of Tan IIA-NPs and free-Tan IIA on tPA and PAI-1 were measured in vitro in TGF-β1-induced HMrSV5 cells. Tan IIA-NPs exhibited small particle size, high encapsulation efficiency, good stability for storage, and safety for intravenous administration. Tan IIA-NPs were effective in preventing adhesion. Tan IIA-NPs increased tPA activity in peritoneal lavage fluid, and tPA mRNA and protein expression, and decreased PAI-1 mRNA and protein expression in the ischemic tissues. Moreover, Tan IIA-NPs decreased TGF-β1 and collagen I expressions in the ischemic tissues. Tan IIA-NPs administered via tail veins upregulated fibrinolysis in the peritoneum. In vitro studies showed that these effects may be mediated by the TGF-β signal pathway.
authors.affiliation: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Qin
authors.affiliation: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Yuanyi
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Pharmacology, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Chuqi
authors.initials: C
authors.lastname: Hou
authors.affiliation: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Si
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Lianbing
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Pharmacology, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.
authors.forename: Chengxi
authors.initials: C
authors.lastname: Wang
mesh_terms: D045784:Abietanes / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D061605:Administration, Intravenous; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005342:Fibrinolysis / Q000187:drug effects; D008297:Male; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010532:Peritoneal Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D011183:Postoperative Complications / Q000473:pathology / Q000517:prevention & control*; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D000267:Tissue Adhesions / Q000517:prevention & control; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D045784:Abietanes; D017395:Plasminogen Activator Inhibitor 1; D053773:Transforming Growth Factor beta1; C021751:tanshinone; D010959:Tissue Plasminogen Activator
keywords: peritoneal fibrinolysis; plasminogen activator inhibitor-1; tissue-type plasminogen activator