1.Reduction of inflammatory-related factor expression in experimental acute pancreatitis in Egr-1 knockout mice
Youcai DUAN ; Bo JIANG ; Gaofeng MA ; Zhimin XU ; Xiaowen CHEN ; Tianming CHENG ; Yichen DAI ; Xueqing CHEN
Chinese Journal of Pathophysiology 1986;0(04):-
AIM: To observe the effects of Egr-1 gene knockout on the expression of inflammatory-related factors in pancreatic tissue in a mouse acute pancreatitis model.METHODS: The experimental pancreatitis was induced by high-dose of cearulein in wildtype mice and Egr-1 knockout mice.The pancreatitis indexes,such as serum amylase,pancreata edema,and myeloperoxidase(MPO) levels in pancreata and lungs were recorded.The mRNA levels of tissue factor(TF),plasminogen activator inhibitor(PAI-1),monocyte chemoattractant protein(MCP-1),Gro-1,IL-6 and ICAM-1 were measured by quantitative PCR.RESULTS: Contrary to wildtype mice,typical pancreatitis was not induced by high-dose cearulein in the Egr-1 knockout mice,not only markedly reduced edema in pancreata and lungs,but decreased MPO levels in lungs as well were found.Furthermore,the mRNA of TF,PAI,MCAP,ICAM-1 and IL-6 in pancreata were significantly decreased in Egr-1 knockout mice.CONCLUSION: The severity of pancreatitis and lung damage is ameliorated in Egr-1 knockout mice stimulated by high-dosage of cearulein,which was probably mediated by decreasing expression of inflammatory-related factors in pancreata,such as TF,PAI,MCP-1,ICAM-1 and IL-6.
2.Clinical features of cholestatic liver disease of 107 cases
Xin XU ; Yichen DAI ; Shiying XUAN
Journal of Clinical Hepatology 2018;34(11):2364-2367
ObjectiveTo investigate the clinical features of cholestatic liver disease (CLD), and to provide a reference for strengthening the diagnosis and treatment of this disease. MethodsA retrospective analysis was performed for the clinical data of 107 patients who were admitted to Chenggong Hospital Affiliated to Xiamen University from January 2015 to December 2017 and were diagnosed with CLD. The t-test was used for comparison of continuous data between groups. ResultsMost patients had the clinical symptoms of weakness, loss of appetite, nausea, abdominal distension, pruritus, and jaundice. According to the site of cholestasis, there were 64 patients (59.8%) with intrahepatic cholestasis and 43 (40.2%) with extrahepatic cholestasis. The cause of the disease was common bile duct stones in 21 patients (19.6%), bile duct parasites in 1 patient (0.9%), primary sclerosing cholangitis in 2 patients (1.9%), primary biliary cirrhosis in 3 patients (2.8%), liver cancer in 8 patients (7.5%), bile duct carcinoma in 5 patients (4.7%), pancreatic cancer in 4 patients (3.7%), pancreatitis in 12 patients (11.2%), viral hepatitis in 28 patients (26.2%), drug-induced liver injury in 11 patients (10.3%), alcoholic hepatitis in 6 patients (5.6%), nonalcoholic fatty liver disease in 4 patients (3.7%), and autoimmune hepatitis in 2 patients (19%). The CLD patients with underlying diseases had a significantly poorer liver function (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, bile acid, and total bilirubin) than those with CLD alone (t=-3.44, -2.99, -2.42, -4.39, -3.34, and -2.49, all P<0.05). Most of the patients achieved good recovery after liver-protecting, transaminase-lowering, and jaundice clearance treatment. The patients with tumors had poor prognosis. ConclusionCLD has various causes, and its clinical features lack specificity. Clinicians should pay enough attention to this disease.
4.Study on Preparation and Pharmacokinetics of Puerarin Microemulsion Based on Phase Ⅰ Metabolic Regulation
Liping DAI ; Wei LI ; Hongyi ZHUO ; Guirong LIU ; Yan HE ; Yichen HU ; Yu SONG ; Liang ZOU
China Pharmacy 2019;30(11):1459-1464
OBJECTIVE: To prepare puerarin microemulsion with phase Ⅰ metabolic regulation (R-PR-ME) and to study pharmacokinetic characteristics of rats in vivo. METHODS: R-PR-ME and Puerarin microemulsion without metabolic regulation (NR-PR-ME) were prepared by Shah method. Pseudo-ternary phase diagram was used to optimize microemulsion formula using drug loading amount as index. The particle size and PDI of microemulsion were characterized by using a laser particle size analyzer. Rats were used as animal models, and HPLC method was used to determine the blood concentration of puerarin before and 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600 min after intragastric administration of R-PR-ME, NR-PR-ME and puerarin suspension (PR-SP) at puerarin dosage of 120 mg/kg. The pharmacokinetic parameters were calculated by using DAS 2.0 software. SPSS 19.0 software was used for statistical analysis. The relative bioavailability of R-PR-ME was calculated with NR-PR-ME as reference preparation. RESULTS: The formula of R-PR-ME included that oleoyl polyoxyl-6 glyserides (oil phase)-polysorbate 20 (emulsifier)-glycerides (co-emulsifier) mass ratio of 2 ∶ 4 ∶ 4; drug-loading amount of 67.50 mg/g, particle size was (22.59±0.53) nm (n=3) and PDI was 0.182±0.017 (n=3). The formula of NR-PR-ME included that soybean oil (oil phase)-polysorbate 80 (emulsifier)- glycerol (co-emulsifier) mass ratio of 1 ∶ 4.5 ∶ 4.5, drug-loading amount of 61.32 mg/g, particle size of (15.45±1.06) nm(n=3) and PDI of 0.156±0.012 (n=3). Pharmacokinetic parameters of R-PR-ME, NR-PR-ME and PR-SP included that AUC0-600 min were (134.187±37.152), (65.145±18.762) and (49.623±12.143) μg·min/mL; cmax were (1.316±0.306), (1.082±0.294) and (0.425±0.106) μg/mL; MRT were (155.068±33.204), (100.264±27.683), (60.524±14.086) min; t1/2β were (365.880±101.250), (283.280±80.940), (80.063±21.189) min (n=6), respectively. Compared with PR-SP, AUC0-600 min, cmax, MRT and t1/2β of R-PR-ME and NR-PR-ME were increased significantly (P<0.05 or P<0.01). Compared with NR-PR-ME, AUC0-600 min, MRT and t1/2β of R-PR-ME were more higher (P<0.05). The relative bioavailability of of R-PR-ME was 205.98%. CONCLUSIONS: R-PR-ME is prepared successfully with high drug-loading amount, and can significantly increase the bioavailability of puerarin in rats, compared with PR-SP and NR-PR-ME.