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Objective:To investigate the effects of propofol on malignant biological behaviors of prostate cancer DU145 cells and its possible mechanism.Methods:Control group, 5-fluorouracil group (200 ng/ml) , low-dose propofol group (100 ng/ml) and high-dose propofol group (400 ng/ml) were set up. CCK-8 kit was used to measure the level of cell proliferation, Transwell method was used to measure the abilities of cell invasion and migration, flow cytometry was used to measure the level of apoptosis, and qRT-PCR and Western blotting were used to measure hepatocyte growth factor (HGF) and c-Met mRNA and protein levels.Results:The survival rates of the control group, 5-fluorouracil group, low-dose propofol group and high-dose propofol group were (83.32±3.02) %, (36.29±3.54) %, (62.01±4.69) % and (40.20±5.48) % ( F=8.65, P=0.006) ; the apoptosis rates were (2.36±0.41) %, (12.47±0.40) %, (6.28±0.39) % and (10.24±0.37) % ( F=26.73, P=0.001) . Further pairwise comparison showed that there were statistically significant differences (all P<0.05) . The numbers of penetrating membranes of the four groups were 617.45±29.86, 125.27±24.38, 407.02±32.27 and 230.74±31.59 ( F=18.33, P=0.002) ; the migration distances were (603.85±27.74) μm, (121.69±25.85) μm, (395.59±28.37) μm and (233.52±30.42) μm ( F=27.02, P=0.001) . Further pairwise comparison showed that there were statistically significant differences (all P<0.05) . HGF mRNA expression levels of the four groups were 6.26±0.39, 1.94±0.35, 4.15±0.37 and 2.90±0.33 ( F=25.31, P=0.001) ; c-Met mRNA expression levels were 5.85±0.30, 2.04±0.32, 3.89±0.31 and 2.94±0.32 ( F=12.12, P=0.003) ; HGF protein expression levels were 1.43±0.04, 0.34±0.08, 0.86±0.06 and 0.63±0.09 ( F=17.02, P=0.001) ; c-Met protein expression levels were 1.63±0.14, 0.39±0.15, 0.93±0.11 and 0.64±0.17 ( F=19.89, P=0.001) . Further pairwise comparison showed that there were statistically significant differences (all P<0.05) . Conclusion:Propofol has obvious inhibitory effects on the malignant biological behaviors of prostate cancer DU145 cells, and the inhibitory effect of high-dose propofol is more obvious. The mechanism may be related to the inhibition of HGF and c-Met mRNA and protein expressions of DU145 cells by propofol, which inhibits the activation of HGF/c-Met pathway.
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Objective Animal experiment is indispensible for the progress of medicine and medical research.Experimental animals deserve basic respect and care.This paper reviewed the history and status of the experimental animal welfare nationally and internationally to identify the ethical problems existed in animal experiments,and finally discuss the establishing of ethical review system of experimental animals.Methods According to literature review,as well as summarizing the operating practice in the affiliated hospital of Chengdu university of TCM,this study analyzed the problems in the field of experimental animal welfare protection.Results Many countries,such as Britain,Germany and the United States,have legislation on the welfare of experimental animals.There are no such laws in China while departmental regulations has formulated.At present,the weak cognition of bioethics among medical personnel,lack of corresponding certification system,lack of the ethical review system of laboratory animal are still unsolved problems.This paper summarizes the principles of ethical review,the documents of review and the elements of review.Conclusions The protection of experimental animals is a systematic project,and ethical review as the first link of animal experiments can play a good role in promoting animal experiment.
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Objective To investigate the protective effect of quercetin on diabetic nephropathy and to explore its possible mechanism.Methods Type 2 diabetes mellitus rat model was established by feeding high-carbonhydrate-fat diet and injecting with streptozotocin.At 72 hour after injection,blood samples were collected from the tail veins of all rats.Those rats with blood glucose level ≥ 16.7 mmol/L were considered as the diabetes model been successfully established.The model rats were randomly divided into type 2 diabetic group ( group DM,n =9 ) and quercetin group ( group QUE,n =9 ).Other rats were used as normal controls (group NC,n =8).All rats were performed by intragastric administration for 8 weeks.At the end of experiment,the rats were sacrificed and fasting plasma glucose( FPG),fasting insulin( Flns),serum creatinine (SCr),blood urea nitrogen(BUN),TG,TC,LDL-C,24 h urine protein (24 h UP),and kidney index ( KI ) were evaluated.Pathological changes of kidney were observed by periodic acid-silver metheramine( PASM ).The expressions of ubiquitin and NF-κB p65 on glomeruli w ere examined by immunohistochemical method,and its association with the incidence of proteinuria was analyzed.Results In groups DM and QUE,the level of FPG [ ( 25.45 ± 1.23 ) mmol/L and ( 19.99 ± 1.20 ) mmoL/L],FIns [ ( 25.67 ± 2.58 ) mU/L and ( 19.29 ± 1.80 ) mU/L ],SCr[ ( 44.00 ± 2.53 ) μmol/L and ( 34.43 ± 2.23 )μmol/L],BUN[ ( 11.60 ± 0.39 )mmol/L and (8.20 ± 0.37) mmoL/L],TG [ (3.32 ± 0.22 ) mmol/L and (2.43±0.25)mmol/L],TC[(2.95 ±0.21) mmol/L and (2.24 ±0.17)mmol/L],LDL-C[(2.03 ±0.22 ) mmol/L and ( 1.49 ± 0.13 ) mmol/L ],24 h UP [ ( 46.67 ± 2.50 ) mg/24 h and ( 25.57 ± 2.82 )mg/24 h]and KI[ (9.76 ±0.30) × 103 and (8.44 ±0.26) × 103 ] were significantly increased than the indexes of group NC [ (6.56 ± 0.41 ) mmol/L,( 12.63 ± 1.41 ) mU/L,( 22.88 ± 2.36 ) μmol/L,( 5.45 ±0.51 ) mmoL/L,( 1.64 ± 0.1 1 ) mmol/L,( 1.33 ± 0.17 ) mmol/L,(0.46 ± 0.05 ) mmol/L,( 12.38 ±1.19)/24 h and (6.78 ±0.12) × 103].Moreover,the above indexes in group QUE were obviously lower than group DM.There was evidence of pathological changes associated with diabetes,such as focal and segmental sclerosis and thickened basement and mesangial expansion.The expressions of ubiquitin and NF-κB p65 in renal tissues of group DM increased significantly ( P ＜ 0.01 ).The expression of ubiquitin and NF-κB p65 were positively related with the level of 24 h UP ( r =0.893,0.879,P ＜ 0.01 ).Compared with group DM,all above indexes in group QUE were markedly alleviated ( P ＜ 0.01 ).The expression of ubiquitin and NF-κB p65 was reduced but didn't reach level in group NC ( P ＜ 0.01 ).Conclusion The increased expression of NF-κB induced by ubiquitin-proteasome system may participate in the pathogenesis of proteinuria in diabetic nephropathy.Quercetin has renal protective effects partly through reducing NF-κB p65 expression.
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The effects of pioglitazone on the expressions of hypoxia-inducible factor-1 α (HIF-1 α) and vascular endothelial growth factor (VEGF) in renal tissues of diabetic rats were observed. Diabetic rat model was established by feeding high-carbonhydrate-fat diet and injecting streptozotocin. After the treatment with pioglitazone, the kidney index, 24 h urinary albumin, blood urea nitrogen, serum creatinine, fasting blood glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), total cholesterol,triglycerides, and low-density lipoprotein-cholesterol of diabetic rats were significantly lower than those of untreated ones, high-density lipoprotein-cholesterol was increased, the expressions of HIF-1α and VEGF in renal tissue were decreased ( all P＜0. 01 ). It suggested that pioglitazone may improve renal function and the balance of glucose-lipid metabolism in diabetic rats via down-regulating HIF-1/VEGF pathway.