| Objective: To investigate the preventive,therapeutic effects and its possible mechanism of trace element strontium alleviating lipid metabolism disorder in non-alcoholic fatty liver disease(NAFLD)rats.Methods: 1.To set up and evaluate the rat NAFLD model: 32 male SD rats were conventional fed by ordinary diets for one week,then randomly divided into four groups: the blank control group,the M1 group,the M2 group and the M3 group.The blank control group rats were fed with ordinary diets,and meanwhile other three groups were fed with high fat diets for various duration(M1 group 5 weeks,M2 group 7 weeks,blank control group & M1 group 9 weeks,).The hepatic tissue of rats were fixed,embedded with paraffin and sectioned.Then the sections were stained by HE staining to observe the pathological changes of liver.2.Group Experiment: 50 male SD rats were conventional fed by ordinary diets for one week,then randomly divided into five groups: the control group,the NAFLD group,the Sr18 group,the Sr36 group and the SIMVA group.The control group rats were fed with ordinary diets,and meanwhile other groups were fed with high fat diets.From the 6th week,rats in the Sr18 group and the Sr36 group were separately fed with the strontium water with concentration of 18mg/L and 36mg/L.And these two groups were separately given strontium water(0.054mg/kgBW ?0.108mg/kgBW)by gavage from the 11 th week,while the SIMVA group were given simvastatin(10mg/kgBW)by gavage from the 11 th week.Rats in other groups were given matching normal saline by gavage in the same time.At the end of the 14 th weeks,all rats were killed and weighed.Then take the blood to measure the contents of ALT,AST,TG,TC,LDL-C and HDL-C in serum.The liver was isolated,weighed and the liver indexes were calculated.Part of right hepatic lobe were homogenized into the 10% tissue suspension for detecting of TC & TG.Same part of right hepatic lobe were embedded with OTC and then prepared into frozen sections.The lipid accumulation in liver sections was tested by oil red O staining.Hepatic lobe were embedded with paraffin and sectioned.The expressions of GRP78,SREBP-2,HMGCR and LDLR in the liver tissue sections were detected with immunohistochemistry.Results: 1.Evaluating of rat NAFLD model: HE staining of hepatic tissue showed that the structure of hepatic lobules was complete,the liver cells were arranged by rule,and hepatic plates went around the central vein radially in the blank control group.The liver cells were arranged by rule,and with a little fatty degeneration in liver cells in the M1 group.The spacing of the liver cells were widen,and with more fatty degeneration in liver cells in the M2 group.The liver cells had irregular arrangement and with the severest fatty degeneration in the M3 group.2.Group Experiment:(1)The TC and LDL-C level of serum in the NAFLD group was statistically higher than that of the Control group(P<0.05).The level of serum TC & LDL-C in the Sr18 group and Sr36 group were statistically lower than that of the NAFLD group(P<0.05).The liver index of rats in the other four groups were higher than that of the control group(P<0.05).The liver index of rats in the Sr36 and SIMVA groups were lower than that of the NAFLD group(P<0.05).The TC and TG level of liver r in the Control group,Sr36 group and SIMVA group was statistically lower than that of the NAFLD group(P<0.05).(2)ORO staining showed that the lipids accumulation in liver increased abnormally in NAFLD group compared to the control group,while it decreased obviously in the Sr18 and Sr36 groups,especial in the SIMVA group,compared with NAFLD group.(3)Immunohistochemistry demonstrated that the expression of GRP78,SREBP-2 and HMGCR increased abnormally in the NAFLD group compared to the control group(P<0.05).The expression of GRP78,SREBP-2 and HMGCR decreased obviously in the Sr36 compared with NAFLD group(P<0.05),while the expression of GRP78 and HMGCR decreased obviously in the SIMVA groups compared with NAFLD group(P<0.05).The expression of LDLR in the other four groups were increased than that in the control group(P<0.05).Compared with NAFLD group,the expression of LDLR in the Sr36 group were increased significantly(P<0.05).Conclusion: 1.The disorder of lipid metabolism in rats with nonalcoholic fatty liver disease should be alleviated by the ingestion of trace element strontium for a long time.2.Its mechanism maybe result from the regulation of strontium on endoplasmic reticulum stress,activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and function of low density lipoprotein receptor. |
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