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OBJECTIVE:To study the preventive effect of resveratrol on model mice and improvement effect on model golden hamsters (shorter for hamsters) with hyperlipidemia. METHODS:Hyperlipidemia animal models were induced by using high-fat and high-cholesterol diet. Mice and hamsters were both randomly divided into model group and resveratrol low-dose, medi-um-dose,high-dose groups(40,80,160 mg/kg for mice,25,50,100 mg/kg for hamsters),10 in each group. 10 corresponding animals were selected as normal control group. Except that normal control group was fed normal diet and intragastrically administrat-ed normal saline,other mice were intragastrically administrated relevant medicines when fed high-fat and high-cholesterol diet;oth-er hamsters were firstly modeled for 2 weeks and intragastrically administrated relevant medicines after modeling. High-fat and high-cholesterol diet was fed during administration. It was administrated for 4 weeks. Total cholesterol(TC)and low density lipo-protein cholesterol(LDL-C)levels in serum of mice and hamsters were detected every week. After 4 weeks,pre-protein converting enzyme subtilisin 9(PCSK9)mRNA and protein expression,microRNA-27a(miRNA-27a)expression in serum of mice and ham-sters,and low density lipoprotein receptor(LDLR)protein expression in liver tissue of mice were detected. RESULTS:Compared with normal control group,the TC,LDL-C,PCSK9 mRNA and protein,miRNA-27a levels of mice in model group were obvious-ly increased after 2 weeks of administration (P<0.05);LDLR protein level in liver tissue was obviously decreased (P<0.05). TC,LDL-C,PCSK9 mRNA and protein,miRNA-27a levels of hamsters in model group were obviously increased (P<0.05). Compared with model group,above-mentioned indexes of mice and hamsters in each administration group were obviously im-proved(P<0.05),which were positively correlated with dose. CONCLUSIONS:Resveratrol has preventive effect on model mice and improvement effect on model golden hamsters with hyperlipidemia. The mechanism may be down-regulating miRNA-27a ex-pression and PCSK9 protein expression in serum,to increase LDLR protein level in liver tissue,and finally reduce LDL-C level.
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Objective: To explore the role of clinical pharmacists in the treatment of artial fibrillation complicated with digoxin poisoning and the entry points of pharmaceutical care.Methods: Clinical pharmacists participated in the therapy for a patient with atrial fibrillation and digoxin poisoning, monitored the blood concentration of digoxin combined with the characteristics of the patient, analyzed the causes of digoxin poisoning in terms of the underlying diseases, renal function and combined medication, and performed beneficial pharmaceutical care.Results: The suggestions of clinical pharmacists were adopted by doctors, digoxin was withdrawn timely and the drug poisoning was corrected.
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AIM:To observe the effects of liraglutide on the level of microRNA-33 (miR-33) and the expres-sion of AMP-activated protein kinase ( AMPK ) and apoptosis-related proteins in mice with type 2 diabetes mellitus (T2DM), and to explore its possible mechanism .METHODS:High-fat diet and intraperitoneal injection of streptozocin were used to establish the type 2 diabetic model in C57BL/6 mice.The mice were randomly divided into 4 groups ( n=15 ):in control group , the normal mice were subcutaneously injected with equivalent volume of saline ;in model group , the T2DM mice were subcutaneously injected with equivalent volume of saline ; in low-and high-dose liraglutide treatment groups, the T2DM mice were subcutaneously injected with 100 and 200 μg? kg -1? d-1, respectively.After 4 weeks of administration, the levels of FBG, TG, TC, HDL-C, LDL-C, ALT and AST were determined.HE staining was used to ob-serve the pathological changes of the liver tissues .The protein level of cleaved caspase-3 in the liver tissue was detected by the technique of immunofluorescence .The protein levels of p-AMPK/AMPK and apoptosis-related proteins were detected by Western blot .The expression of miR-33 in the liver tissues was detected by real-time PCR.RESULTS: Compared with model group, the contents of FBG, TG, TC, LDL-C, ALT and AST were decreased significantly , while the content of HDL-C was increased significantly in low-dose liraglutide group and high-dose liraglutide group ( P<0.05 ) .The protein levels of phosphorylated AMPK and Bcl-2 were up-regulated significantly , and the expression of cleaved caspase-3 was down-regulated significantly (P<0.05).The level of miR-33 was decreased significantly (P<0.01).CONCLUSION:Liraglutide alleviates liver injury in type 2 diabetic mice , and the mechanism may be associated with reducing the level of miR-33 and increasing the phosphorylation of AMPK in the liver tissues , thereby inhibiting hepatocyte apoptosis .
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AIM: To observe the therapeutical effects of resveratrol on non-alcoholic fatty liver disease and its potential mechanism.METHODS: Male C57BL/6J mice were fed with high-fat and high-cholesterol diet to established non alcoholic fatty liver disease model, and were administrated with resveratrol at doses of 80 mg/kg and 160 mg/kg.After 4-week treatment, the blood sample was collected for determination of total cholesterol (TC) and triglyceride (TG).The liver tissues were harvested for measuring the liver lipid content.The histopathological examination were conducted with hematoxylin and eosin staining.The ceramide levels in the liver tissues were detected by HPLC-MS.The microRNA (mi-RNA)-122 levels in the liver tissues were detected by real-time PCR.The protein levels of serine palmitoyltransferase (SPT) were determined by Western blot.The HepG2 cells were cultured and divided into 5 groups: control group, model group (induced by 0.25 mmol/L oleic acid), model+resveratrol group (treated with 5 μmol/L resveratrol), miRNA-122 siRNA group and resveratrol+miRNA-122 siRNA group.Except control group, the cells in other groups were stimulated with oleic acid and incubated with respective drugs simultaneously for 24 h.The levels of TC, TG and ceramide in the cells of each group were measured.The protein levels of SPT in each group were determined by Western blot.RESULTS: In non-alcoholic fatty liver disease mice, resveratrol dose-dependently reduced the serum TC and TG levels, decreased the lipid deposition, the ceramide level and the SPT protein level, and increased the level of miRNA-122 in the liver tissues.In the in vitro study, compared with model group, resveratrol reduced the serum TC and TG levels, decreased the ceramide level, reduced the SPT protein level.Compared with control group, the levels of TC, TG and ceramide, and the protein expression of SPT were increased in miRNA-122 siRNA group.Compared with miRNA-122 siRNA group, no statistical difference of TC, TG, ceramide and protein expression of SPT in resveratrol combined miRNA-122 siRNA group was observed.CONCLUSION: Resveratrol significantly reduces lipid accumulation by reduction of miRNA-122 and ceramide levels, and decrease in SPT protein levels in the liver.
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AIM: To observe the anti-apoptosis effect of liraglutide on the islet through microRNA-375 (miR-375) for providing additional pharmacodynamic evidence for its clinical application.METHODS: For in vivo study, C57BL/KsJ-db/m mice aged 8 weeks served as normal control group.A total of 40 male genetically diabetic C57BL/KsJ-db/db mice at the same age were randomly divided into diabetic control group (the db/db mice were injected subcutaneous-ly with equivalent amount of saline) and liraglutide group (the db/db mice were injected subcutaneously with liraglutide at dose of 300 μg? kg-1? d-1 ).After 8 weeks of administration, body weight (BW) was measured and blood was collected for detection of fasting blood glucose (FBG), fasting blood insulin (FINS), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C).Before sacrifice, intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were conducted.The histopathological features in the islet tissue were examined with HE staining.The apoptosis in the islet tissue was detected by TUNEL staining.The protein levels of caspase-3, Bcl-2 and Bax were deter-mined by Western blot.The level of miR-375 in the islet tissue was detected by qPCR.For in vitro study, the MIN-6 cells were cultured and divided into control group (incubated with equivalent amount of solvent), miR-375 mimic group and miR-375 mimic +liraglutide group.The cell viability was examined by MTT assay.The protein levels of caspase-3, Bcl-2 and Bax were detected by Western blot.RESULTS: In the in vivo study, compared with control group, the levels of BW, FBG, FINS, TC, TG and LDL-C were decreased significantly in liraglutide group.The islet apoptosis was reduced by the administration of liraglutide.The expression of Bcl-2 was up-regulated significantly, while the protein levels of caspase-3 and Bax were down-regulated significantly in liraglutide group.The level of miR-375 was decreased significantly.In the in vitro study, the cell viability was decreased in miR-375 mimic group and increased in miR-375 mimic +liraglutide group. Moreover, the expression of Bcl-2 was decreased and the protein levels of caspase-3 and Bax were increased with the incu-bation of miR-375 mimic, while the expression of Bcl-2 was increased and the protein levels of caspase-3 and Bax were de-creased with the co-incubation of miR-375 mimic and liraglutide.CONCLUSION: Liraglutide attenuates islet apotosis, and the mechanism may be associated with its effects of reducing the elevated level of miR-375 in islet tissues.
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The authors observed fifty petrosal veins in twenty five adult specimens with surgical microscope under ten times magnification.Special attentionwas paid to the microsurgical anatomical features of the petrosal vein andthe relations between these features and some aspects of the posterior rhi-zotomy of the trigeminal nerve. There is only one petrosal vein in each half of the specimen in themajority of the cases observed. All petrosal veins can be subdivided into three types: 1 ) single-trunk type; 2 ) two-trunk type; 3 ) three-trunktype. The micro-anatomical features of the vein are as follows: 1 ) in adeep position; 2 ) with a thinnest wall; 3 ) with a thicker and shortertrunk; 4 ) in a free and suspended manner during traversing the subarachnoidspace. During operation, the petrosal vein covered with a thin layer ofarachnoid can be seen. The method of how to sever the vein is different because the formationof it is different. Most of petrosal veins are located at a position superiorlateral to the teminal root, so they can be used as a guidance of looking for the nerve root.