| Luodan Capsule is refined by clinical Chinese medicine commonly used lipid regulatingprescription. In this study, a preliminary evaluation of the security of Luodan capsules is conducted. Andthrough different animal models, the experiment investigated the regulating effects on serum lipid ofhyperlipidemia and the therapeutic effect on fatty liver in rats, which provides scientific basis for itsin-depth study and clinical application.The research is divided into the following sections:1Luodan Capsule safety evaluation experiments Because Luodan Capsule has no obvioustoxicity, the experiment use maximal tolerance dose test（MTD）to evaluate the security of the drug.Method:40KM mice were divided to two groups, each of20male and female. The mice inexperimental group were given with the maximal dose of the drug, while the control group mice receivedequal volume of distilled water, twice a day. After administrated, mental state and death situation of thesemice were observed and recorded, once every4hours on the first day and then twice a day. During thisperiod, changes in body weight of mice were recorded. Results: mental state of some mice in theexperimental group was sluggish on the first day, and the next day returned to normal. All of mice has noother abnormalities. Throughout the course of the experiment, the body weight changes are consistent withthe experimental group and the control group of mice. When the end of the experiment, all animals arehealthy survival, which indicates that the Luodan capsules is safe.2The study of Luodan Capsule regulating blood lipids and treating fatty liver.2.1The effect of regulating blood lipid on normal rats Refer to <Pharmacological ExperimentsMethodology>, normal rats as a model to investigate the impact of drug on blood lipid levels.Method:40normal SD rats were divided into four groups: the normal control group, thehigh-dose group, he middle-dose group and the low-dose group (n=10), half male half female. Aftergrouping, the experimental group rats were began to give the appropriate dose of drugs for a week. After aweek, blood was collected from the orbital venous plexus of all groups of rats and the main Biochemicalparameters were measured．Result: As can be seen from the experimental results, the TC level of experimental group rats was lower than normal group by up to50%, and the LDL levels of middle-dosegroup rats decreased by approximately21.3%. It shows Luodan capsule may has capability that lower TCand LDL levels.2.2The effect of regulating blood lipid on acute hyperlipidemic mice Mice were given a certainamount of egg yolk emulsion by intraperitoneal injection, which can dramatically increased the blood TCand TG level. This model can be used as the initial screening of lipid-lowering drugs.Method:60KM mice were divided into six groups: the normal control group, the model controlgroup, the positive control group, the high-dose, middle-dose and low-dose treatment group（n=10）, halfmale half female. According to the corresponding dose, each group mice were given drug for7days. Inaddition to the normal control group, all of mice were given a certain amount of freshly prepared75%eggyolk emulsion (0.5ml/30g) by intraperitoneal injection. The nest day, blood was clloceted by eyeballs andblood serum was separated and detected. Result: The results show that compared with the normal group,the TC, TG level of the model control group increased greatly and that the model was successful.Compared with the model group, the treatment group mice serum TC and TG levels decreased to a certainextent. It shows that the drug can effectively reduce TC and TG levels.2.3Establishment of chronic hyperlipidemia model To establish the model in the short term byhigh fat and high sugar diet feeding method, not only the lipid levels in vivo increase, but also fatty liver ina certain degree can form.Method:54SD rats were divided into two groups: normal group (n=6) and model group (n=48).The model group rats were given high fat diet, and normal group were given normal diet.4weeks later, themodel group switch to normal diet.6rats of the model group were killed on the1st,2nd,3rd,4th,5th,6th,7th week. Serum was separated and frozen for subsequent detection of TC, TG, ALT and AST. The liverswere divided into two parts, one part fixed with10%formaldehyde solution, for the production ofpathological section; another part frozen, for the detection of TC, TG, MDA and SOD. On the8thweekend of the experiment, all normal rats and the remaining rats in model group were killed, serum andliver were managed in the same way. Result: It can be seen that the level of TC, TG, ALT, and AST inserum of the model group rats increased significantly（P＜0.05or P＜0.01）after4weeks. The level of TC,TG, MDA in liver was also increased and the level of SOD was decreased significantly. It can be found that the model group rats formed fatty liver obviously. Switched to normal diet for4weeks, the level of resumlipid and liver fat accumulation in the model group declined, but still there is a significant differencebetween the normal and model group. Therefore, the model can be used as the basis of laterpharmacodynamic studies.2.4The effect of Luodan Capsule on chronic hyperlipidemic fatty liver After established thehyperlipidemia model by high-fat diet, the experimental rats were began to receive drug. The purpose is toexamine the impact of drugs on the blood lipid levels and the fatty liver in experimental animals.Method:60male rats were divided into two groups: the normal group (n=10) and the modelgroup (n=50). The model group rats were given high-fat diet, while the normal group rats normal diet.When the model is successfully established, the model group was divided into five groups: the modelcontrol group, the positive control group, the high, middle and low dose group(n=10). The experimentalgroup switched to normal diet, and was given appropriate dose of the drug. After4weeks, the rats werekilled. The serum separated and the livers removed were saved for detecting biochemical indicators ormaking pathological section. Result: Compared with the model group, the level of TC, LDL, ALT, and ASTin serum of the high, middle, low dose group were significantly reduced, and the level of SOD wasincreased obvious (P＜0.05or P＜0.01). The fat accumulation in liver also significantly decreased. Theexperimental results show that Luodan Capsule has the capability of regulating blood lipid and improvingfatty liver.2.5The exploration of LuoDan capsule lipid-lowering mechanisms According to theexperimental results of the past，the levels of HMGR、LCAT and LPL\HL in serum and liver were selectivedetected to find out the mechanism of regulating blood lipid.Method: the levels of HMGR, LCAT and LPL, HL were separately detected by ELISA kit andLPL/HL kit. RESULTS: the HMGR level in serum of rats in treatment group decreased to varying degrees,and there is a significant difference; LCAT levels also increased significantly; and LPL/HL content in liverhad no obvious change, The experimental results suggest that Luodan Capsule’s regulating blood lipid andtreating fatty liver may be achieved by inhibiting the activity of HMGR to reduces endogenous cholesterolsynthesis and increasing the activity of LCAT to promote the metabolism of cholesterol3Conclusion: In summary, Luodan Tiaozhi Capsule not only has high security, but also has a therapeutic role for hyperlipidemia and fatty liver. |
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