| Objective: To observe the effect of Zexie-Decoction on the content ofTC, TG, HDL-C and LDL-C in blood serum of hyperlipidemia (HLP) rats; Toinvestigate the influence of Zexie-Decoction on the expression ofLXRαmRNA in liver and its down stream gene CYP7A1mRNA in liver andABCA1in liver and small intestine; Further to discusse the therapeutic effectof Zexie-Decoction on HLP and its possible mechanism.Methods:50male Sprague-Dawley rats (160-180g) were purchasedfrom the Laboratory Animal Center (Hebei Medical University, China). Ratswere housed in standard rat cages and were exposed to a12-h light:12-h darkcycle. After1week, they were randomly divided into5groups that each grouphad10rats: Normal control group, Model control group, High-dose ofZexie-Decotion group, Low-dose of Zexie-Decotion group, Xue-Zhi-Kangcontrol group. In the next4weeks, rats in normal group were fed withordinary forage, and the others were fed with high-fat forage. At the same time,control drug or treatment drug was given to each group and equal amount ofSaline was given to normal and model groups which lasted for4weeks ofstomach-perfusion. Rats in each group were given stomach-perfusion once aday and the drug volume was calculated by1ml/100g.12hours fasting afterthe last stomach-perfusion, all rats were anaesthetized and their blood weredrawn out from femoral artery, centrifuged, and then isolated the serum inorder to measure the content of TG, TC, HDL-C and LDL-C in blood serum.Simultaneously, the liver was obtained quickly and portion hepatic tissue wasremoved in right lobe of liver, and then frozen in-70℃for testing theexpression of LXRαmRNA and CYP7A1mRNA. At the same time, suitablesize of hepatic tissue and small intestine tissue were removed, soaked in4%paraform, paraffin imbedding, slice, HE stained to provide for the observation of the light microscope. What is more, we observed the expression changes ofABCA1in liver tissue and small intestine tissue with the immune chemicalmethod.Results：1Changes of content of TC, TG, HDL-C and LDL-C in serum of HLPratsCompared with normal group, the contents of TC, TG and LDL-C inserum of model group (4.55±0.42,2.58±0.29,2.95±0.31) were obviouslyincreased (1.78±0.21,0.79±0.08,0.67±0.09)(P <0.01), and the content ofHDL-C (0.42±0.05) was obviously decreased (0.84±0.08)(P <0.01), whichshowed that HLP rats had significant blood-fat metabolic disturbance. Afterthe intervention of medicine, every treatment group could significantly reducethe content of TG, TC and LDL-C (P <0.01), and increase the content ofHDL-C (P <0.01). Among the total, the content of TC in control group andhigh-dose group (2.32±0.39,2.23±0.30) were obviously lower than low-dosegroup (3.35±0.26)(P <0.01). The content of TC in high-dose group had nostatistical significance with control group（P>0.05）. The content of TG incontrol group (1.17±0.12) was significantly lower than high-dose andlow-dose groups (1.24±0.11,1.70±0.20)(P <0.01), and high-dose group lowerthan low-dose group (P <0.01). There were no marked difference betweenhigh-dose group, low-dose group and control group of the content of HDL-C(0.71±0.08,0.69±0.07,0.75±0.10)(P>0.05).The content of LDL-C inlow-dose groups (1.82±0.21) were higher than control group and high dosegroup (1.11±0.17,1.13±0.19)(P <0.01). There was no marked differencebetween control group and high-dose group of the content of LDL-C (P>0.05).2Changes of liver tissue morphology of HLP ratsIn normal group, the structure of hepatic lobules and hepatic sinusoidwere clear, hepatic cells arranged orderly and distributed as radial aroundcentral veins. The nuclear form was normal, cytoplasm were well-distributed.As for the rats in model group, the hepatic cells arranged disordered and in different sizes. There also appeared obviously fatty degeneration: a lot ofdifferent sizes lipid droplets inside the cytoplasm, furthermore, the nucleusdeviated from the normal position. Compared with the model group, thepathological changes in each treatment group were ameliorated in varyingdegree. The number of lipid droplets and adipose hollow space were decreasedobviously, the structure of hepatic lobules and hepatic sinusoid was clearerand the fatty degeneration was improved significantly than model group.3Changes of expression of LXRαmRAN in hepatic tissue of HLP ratsCompared with normal group (0.369±0.030), the expression ofLXRαmRAN in model group (0.634±0.039) were markedly degraded(P<0.01). After the intervention of medicine, each treatment could strengthenthe expression of LXRαmRAN (P <0.01). The expression of LXRαmRAN inhigh-dose group and low-dose groups (0.677±0.060,0.668±0.039) wereobviously higher than control group (0.563±0.038)(P <0.01), and there wasno statistical significance between those two groups (P>0.05).4Changes of expression of CYP7A1mRAN in hepatic tissue of HLP ratsCompared with normal group (0.767±0.031), the expression ofCYP7A1mRAN in model group (0.316±0.042) were markedly degraded (P<0.01). After the intervention of medicine, each treatment could strengthen theexpression of CYP7A1mRAN (P <0.01). The expression of CYP7A1mRANin high-dose group and low-dose groups (0.645±0.029,0.624±0.018) wereobviously higher than control group (0.492±0.025)(P <0.01), and there wasno statistical significance between these two groups (P>0.05).5Changes of expression of ABCA1in hepatic tissue of HLP ratsLight microscope observation: ABCA1were expressed in hepaticcytoplasm and showed yellow brown. In normal group, the yellow brownparticles were widely distributed and stained darker. In model group, theyellow brown particles were scattered and stained lighter. After theintervention of medicine, each treatment group could make the number of theyellow brown particles increased and the stain darker in different degree.Semi-quantitative analysis observation: Compared with normal group (0.323±0.031), the expression of ABCA1in model group (0.120±0.019)were markedly degraded (P <0.01). After the intervention of medicine, eachtreatment could strengthen the expression of ABCA1(P <0.01). Theexpression of ABCA1in high-dose group and low-dose groups (0.390±0.032,0.377±0.043) were obviously higher than control group (0.288±0.030)(P <0.01), and there was no statistical significance between those two groups(P>0.05).6Changes of expression of ABCA1in small intestine tissue of HLP ratsLight microscope observation: In small intestine tissue, ABCA1wereexpressed in cytoplasm of epithelial cells and macrophages, and showedyellow brown. In normal group, the yellow brown particles were widelydistributed and stained darker. In model group, the yellow brown particleswere scattered and stained lighter. After the intervention of medicine, eachtreatment group could make the number of the yellow brown particlesincreased and the stain darker in different degree.Semi-quantitative analysis observation: Compared with normalgroup(0.426±0.016), the expression of ABCA1in model group (0.180±0.020) were markedly degraded (P <0.01). After the intervention of medicine,each treatment could strengthen the expression of ABCA1(P <0.01). Theexpression of ABCA1in high-dose group and low-dose groups (0.390±0.032,0.377±0.043) were obviously higher than control group (0.288±0.030)(P<0.01), and there was no statistical significance between those two groups (P>0.05).Conclusions:1Zexie-Decotion could significantly reduce the content of TC, TG andLDL-C, and increase the content of HDL-C in serum, showing that it hadsatisfactory function in regulating blood fat and improving disorder of bloodfat.2Zexie-Decotion could obviously improve the lesion degree of livertissue of HLP rats, it manifested like this: after the drug was given, the fattydegeneration improved significantly, the number of lipid droplets and adipose hollow space decreased obviously,.3Zexie-Decotion could strength the expression LXRαmRAN in hepatictissue, promote conveying of lipid and metabolism of cholesterol, meanwhile,it could reduce the liver fat deposition in hepatic tissue, ease and preventhepatic fat pathological changes.4Zexie-Decotion could strength the expression of CYP7A1mRAN inhepatic tissue, promote cholesterol transform into bile acid, and enhancemetabolism and excretion of cholesterol to achieve the purpose of curing theHLP.5Zexie-Decotion could strength the expression ABCA1in hepatic tissueand in small intestine tissue, thus it could promote reverse cholesteroltransport, restrain the absorption of cholesterol. In this way, Zexie-Decotioncould achieve the purpose of improving the cholesterol level of HLP. |
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