Effect of Astragaloside Ⅳ in Regulating PI3K/Akt/FoxO1 Pathway and Inhibiting Hepatic Gluconeogenesis in Diabetic Rats / 中国实验方剂学杂志

<b>Objective::To investigate the potential mechanism of astragaloside Ⅳ in protecting liver injury and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/forkheadbox transcription factor 1 (FoxO1), phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase) protein expressions in type 2 diabetic (T2DM) rats. <b>Method::After 6 weeks of high-sugar and high-fat diet, a model of type 2 diabetes was established through intraperitoneal injection of streptozotocin (STZ, 0.035 g·kg^-1). The rats were randomly divided into normal group, model group, low, medium and high-dose astragaloside Ⅳ groups and metformin group, 0.02, 0.04, 0.08 g·kg^-1·d^-1 astragaloside crude drug and 0.2 g·kg^-1·d^-1 metformin were administered in the low, middle and high-dose astragaloside Ⅳ and metformin groups. After 8 weeks of continuous administration, and 24 hours later after the last gavage, the rats were executed. Serum and liver tissues were collected to detect serum liver biochemical indexes, liver index HDL-C. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of liver tissue. Masson staining was used to observe the degree of liver fibrosis. The changes of glycogen, glycoprotein, or mucopolysaccharide in tissue cells were observed by periodic acid Schiff (PAS) reaction staining. Immunohistochemistry and Western blot analysis were used to detect the expression levels of PI3K/Akt/FoxO1 signaling protein and PEPCK and G6Pase in liver tissues of each group. <b>Result::Compared with normal group, the liver index of the model group increased significantly (<italic>P</italic><0.01), the levels of liver function indicators alanine aminotransferase(ALT), aspartate aminotransferase(AST), TC and TG were significantly increased (<italic>P</italic><0.01), while HDL-C and body weight were significantly reduced (<italic>P</italic><0.01). The results of immunohistochemistry and Western blot showed that the signal of PI3K/Akt/FoxO1 was weakened (<italic>P</italic><0.01), and PEPCK and G6Pase were increased (<italic>P</italic><0.01) in model group. Compared with model group, the contents of ALT, AST, TC and TG in middle and high-dose astragaloside Ⅳ groups were significantly decreased (<italic>P</italic><0.05, <italic>P</italic><0.01), while the body weight was significantly increased (<italic>P</italic><0.05, <italic>P</italic><0.01), the middle and high dose of astragaloside Ⅳ significantly inhibited the levels of FoxO1, PEPCK and G6Pase in liver tissue (<italic>P</italic><0.05, <italic>P</italic>< 0.01), and enhanced the phosphorylation of FoxO1 (<italic>P</italic><0.05, <italic>P</italic><0.01). <b>Conclusion::Astragaloside Ⅳ may inhibit T2DM hepatic gluconeogenesis by regulating PI3K/Akt/FoxO1 signaling pathway, and inhibiting high-fat, high-sugar and low-dose STZ, thereby protecting liver damage in T2DM rats.

The associations of polymorphism of N-acetyltransferase 2 gene is associated with antituberculosis drug-induced hepatotoxicity in tuberculosis patients / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the possible relationship between polymorphic N-acetyltransferase 2 (NAT2) acetylator status and antituberculosis drug-induced hepatotoxicity and to elucidate the molecular mechanism of antituberculosis drug-induced hepatotoxicity.</p><p><b>METHODS</b>Blood samples from 101 tuberculosis cases with antituberculosis drug-induced hepatotoxicity and from 107 tuberculosis without antituberculosis drug-induced hepatotoxicity were collected for a case-control study. DNA of the subjects was extracted and amplified by polymerase chain reaction (PCR). The single nucleotide polymorphisms of NAT2 were determined by direct PCR sequencing. The genotype frequencies were compared between cases and controls by χ(2) test, using SPSS 12.0 software, and the association between the disease and genotypes was analyzed.</p><p><b>RESULTS</b>Among the 101 patients with antituberculosis drug-induced liver injury, 36 patients (35.6%) were found with 282 T/T, 12 (11.9%) with 590 A/A, and 48 (47.5%) with 857 G/A or A/A. However, among the 107 controls, 9 patients (8.4%) were found with 282 T/T, 3 (2.8%) with 590 A/A, and 33 (33.8%) with 857 G/A or A/A. The patients with 282 T/T, 590 A/A, or 857 G/A or A/A genotype had a higher risk of antituberculosis drug-induced hepatotoxicity than those with 282 C/C or C/T, 590 G/G or G/A, or 857 G/G, and the OR values were 6.03 (95%CI: 2.88 - 12.62; χ(2) = 22.73, P < 0.05), 4.67 (95%CI: 1.42 - 15.44; χ(2) = 6.40, P < 0.05) and 2.03 (95%CI: 1.16 - 3.57; χ(2) = 6.08, P < 0.05) respectively. There were 40 patients with slow acetylator (39.6%) in cases with hepatotoxicity and 13 with slow acetylator (12.2%) in controls without hepatotoxicity. Patients with slow acetylator genotype (OR = 4.74, 95% CI = 2.42 - 9.28; χ(2) = 20.62, P < 0.05) had a significantly higher risk of antituberculosis drug-induced hepatotoxicity than those with rapid or intermediate acetylator genotypes. Among the cases, 19.8% (20/101) were found with NAT2(*)6A/7B, and 11.9% (12/101) with NAT2(*)6A/6A, whereas among the controls, 2.8% (3/107) were found with NAT2(*)6A/7B, and 2.8% (3/107) with NAT2(*)6A/6A respectively, the patients with NAT2(*)6A/7B and NAT2(*)6A/6A had a much higher risk of antituberculosis drug-induced hepatotoxicity, and the OR values were 8.40 (95%CI: 2.85 - 24.73; χ(2) = 14.90, P < 0.05) and 4.67 (95%CI: 1.42 - 15.44; χ(2) = 6.40, P < 0.05) respectively.</p><p><b>CONCLUSION</b>Perhaps, the slow acetylation genotypes of NAT2 were the main risk factors of developing antituberculosis drug-induced hepatotoxicity.</p>

Complete sequence of the M segment of Amur virus in rodent from China / 中华流行病学杂志

Objective To study the complete sequence of M segment of Amur virus in rodents and to explore their molecular characteristics. Methods Complete M segment of Amur virus in rodent from China was amplified by RT-PCR. The purified PCR product was cloned into pGEM-T Easy vector and then sequenced. Phylogenetic analysis on multiple nucleotide sequences was performed with the Tree PUZZLE and DNAStar software. Results The full-length of its M gene comprised of 3615 nucleotides with one open reading frame (ORF) including 3408 nucleotides and encoding a protein which comprised 1135 amino acids. The ORF was located at bases 41 to 3448. The phylogenetic analysis of JilinAP06 with other hantaviruses revealed that the complete sequence of M segment of JilinAP06 strain was closely related to those Amur viruses such as B78 strain, Liu strain and H5 strain were all from the patients. The complete sequence of M segment of JilinAP06 had only 79.5% identities with the nucleotide sequence of HTNV strain 76-118. Conclusion The complete sequence on M segment of Amur virus in rodent was first time identified in this country.