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Objective To study the relationship between phosphodiesterase 4D (PDE4D) gene rs966221 single nucleotide polymorphisms (SNPs) and ischemic stroke (IS) in Guangxi Zhuang population.Methods One hundred and one IS patients from Guangxi Zhuang Autonomous Region served as IS pgroup and 104 healthy subjects undergoing physical ecamination served as control group in this study.Their PDE4D gene rs966221 SNPs were detected by SNaPshot technique.The genotypes and frequencies of alleles were compared between the two groups and the relationship between PDE4D gene rs966221 SNPs and IS was analyzed.Results No significant difference was found in the GG,GA,AA genotypes and in the frequencies of G and A alleles between the two groups (0.99％ vs 3.85％,29.70％ vs 21.15％,69.31％ vs 75.00％,P＞0.05;15.84％ vs 14.42％,84.16％ vs 85.58％,P＞0.05).Univariate and multivariate logistic regression analysis showed that the PDE4D gene rs966221 SNPs were not related with the risk of IS in dominant AA vs GG+GA,recessive GG vs AA+GA and additive GG vs AA genetic models (P＞0.05).Conclusion The PDE4D gene rs966221 SNPs are not related with IS in Guangxi Zhuang population.
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Objective To investigate the glucolipid metabolism in lipoprotein lipase (LPL) gene knockout mice, and to explore the possible mechanisms of insulin resistance. Methods 16- and 40-week old LPL gene knockout heterozygous mice( LPL + / -) and wild type ( WT) C57 mice were selected and divided into 4 groups:16-week LPL+ / -(n=6), 16-week WT(n = 6), 40-week LPL+ / -(n = 6), and 40-week WT(n = 6) group. LPL activity of post-heparin serum was examined. Serum triglyceride( TG) and free fatty acid( FFA) were measuzed. Intraperitoneal glucose tolerance test(IPGTT) in 4 groups of mice were performed. The glucose area under the curve (AUCG) and homeostasis model assessment for insulin resistance index and β-cell function index ( HOMA-IR, HOMA-β) were calculated to evaluate insulin sensitivity and the function of islet β-cells. Serum malondialdehyde (MDA) and total antioxidant capacity ( TAOC) levels were determined by means of colorimetric method. Using dihydroethidium( DHE) fluorescent staining method, reactive oxygen species ( ROS) levels in liver and skeletal muscle were determined. Results LPL activity levels of both 16- and 40-week LPL+ / - mice were significantly lower than that in WT mice of the same age. Serum TG and FFA of 40-week old LPL+ / - mice were significantly higher than those in WT mice of the same age(P<0. 05), and they were also higher than those of 16-week old LPL+ / - mice(P<0. 05). IPGTT showed that compared with WT mice, blood glucose level in LPL+ / - mice was significantly higher than that in WT group at 30 and 120 minute(P<0. 05), and fasting insulin and HOMA-IR were increased significantly(P<0. 05). Serum MDA of 40-week old LPL+ / - mice was evidently higher than that in WT mice by the same week(P<0. 05), while TAOC level was lower than that of WT mice (P<0. 05). ROS in skeletal muscle of 16-week old LPL+ /- mice was significantly increased. Meanwhile, ROS in both liver and skeletal muscle of 40-week old LPL+ / - mice was significantly higher than that in WT mice of the same age. Conclusion As time goes by, lipid and glucose disorders of LPL+ / - mice are aggravating, and insulin resistance develops evidently. Insulin resistance in LPL+ / -mice with dyslipidemia may be related to oxidative stress.
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Objective To compare the differences in responsive ability and oxidative stress damage between type 2 diabetic rats and normal rats under acute sepsis associated with stress hyperglycemia.Methods GK rats with type 2 diabetes and Wistar rats were established critical ill models of sepsis by intraperitoneal injection of 5 mg/kg lipopolysaccharide(LPS).Before and after LPS injection,serum levels of proinflammatory cytokines tumor necrosis factor α (TNF-α),interleukin (IL)-1β3,and IL-6,and anti-inflammatory cytokine IL-10 were determined.Malondialdehyde (MDA) and total antioxidative capacity (T-AOC) levels in serum and tissues (lung,liver,kidney,heart) were measured by colorimetric determination.Results Before LPS injection,serum levels of TNF-α,IL-6,and IL-10 in GK rats were higher than those of Wistar rats.The serum levels of TNF-α,IL-6,and IL-10 after LPS injection were raised in both GK rats and Wistar rats (all P＜0.05).At baseline,serum MDA level of GK rats was higher than that of Wistar group [(25.76 vs 12.71) μmol/L,P＜0.05],while T-AOC level were lower [(0.60 vs 2.8) U/ml,P＜0.05].One hour after LPS injection,the serum MDA level in two kinds of rats significantly increased compared with those of their baseline levels [(32.30 and 20.19) μmol/L,both P＜0.05],while their serum T-AOC level decreased [(0.20 and 2.08) U/ml,P＜0.05]).There were no signigicant differences in the change trend of serum MDA and T-AOC between the two kinds of rats.MDA and T-AOC levels in tissues had no significant difference before and after LPS injection in GK and Wistar rats (P＞0.05).Conclusions The rats with type 2 diabetes had lowered level of proinflammatory factors and raised level of anti-inflammatory factors under acute sepsis,presenting better tolerance and lowered probability of inflammatory diffusion compared with normal rats.
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Objective: To investigate the expression of ATP-Binding Cassette Proteins including P-gp (P-glycoprotein), MRP1 (multidrug resistance associated protein 1) and BCRP (breast cancer resistance protein) in hepatocellular carcinoma and its relationship with pathological features. Methods: The expression of P-gp/MDR1 (multidrug resistance gene 1), MRP1 and BCRP in hepatocellular carcinoma was examined by RT-PCR and immunohistochemistry in 34 cases of hepatocellular carcinoma and 19 cases of paraneoplastic hepatic tissues. Results: The expression of MDR1, MRP1 and BCRP mRNA (messenger ribonucleic acid) was 1.15±0.24, 0.64±0.33, and 1.07±0.32 in hepatocellular carcinoma and 0.36±0.14, 0.19±0.06, and 0.31±0.09 in paraneoplastic hepatic tissues. The expression of MDR1, MRP1 and BCRP mRNA was 1.38±0.26, 0.73±0.35, and 1.34±0.21 in poorly differentiated hepatocellular carcinoma and 0.74±0.32, 0.30±0.11, and 0.45±0.13 in well differentiated hepatic tissues. The immunohistochemical positive substance was detected in the plasma membrane and cytoplasm. The positive rates of P-gp, MRP1 and BCRP were 82.35%, 58.82%, and 79.41% in hepatocellular carcinoma and 42.11%, 26.32%, and 36.84% in paraneoplastic hepatic tissues, respectively. The positive rates of P-gp, MRP1 and BCRP were 100.00%, 81.25%, and 100.00% in poorly differentiated hepatocellular carcinoma and 66.67%, 38.89%, and 61.11% in well differentiated hepatic tissues. The expression of three indicies in hepatocellular carcinoma was higher than that in paraneoplastic hepatic tissues (P<0.05). The expression of P-gp/MDR1, MRP1 and BCRP in poorly differentiated hepatocellular carcinoma was higher than that in well differentiated hepatic tissues (P<0.05). No correlation was found among the three indices. Conclusion: Intrinsic multidrug resistance exsists in hepatocellular carcinoma, with various mechanisms. The multidrug resistance of HCC (hepatic cell carcinoma) is related to P-gp/MDR1, MRP1 and BCRP. MRP1 and BCRP may be targets for reversing multidrug resistance.
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Objective To explore the possibility that rat bone mesenchymal cells (BMSCs) can differentiate into hepatocytes under the affection of fetal liver filtrate. Methods PAS and green indigo dye were used to detect glycogen and differential level of hepatocytes, respectively. The concentration of ALT, AST, ALP in the culture supernatant were served as markers of hepaocyte function. Results Fourteen days after induced by the fetal liver filtrate, BMSCs changed their shapes into polygon, oval or round. Some of BMSCs were positive for AFP and ALB at 7 days after induction, then the number of positive cells increased, and most of BMSCs expressed AFP and ALB till 21days. The PAS reaction and indocyanine green(ICG) intaking also appeared at 7days. Enzyme in supernatant such as ALT, AST, ALP were fristly detected at 7days and peaked at 14days,then the level declined. Conclusion The fetal rat liver filtrate was able to induce BMSCs into cells with function and characteristics of hepatocytes.