| Objectives: To investigate the effects of synthetic adrenocorticotropic hormone (ACTH1-24 and ACTH4-10) on serum lipid levels and renal function in Sprague-Dawley rats on normal diet, in order to understand whether SD rats can be used as a ideal research animal models of ACTH1-24 in cholesterol-lowering mechanism ,and to discuss the lipid-lowering mechanism and effect of renal function of ACTH1-24. And to investigate whether ACTH4-10 has the same effect on lipid levels and renal function.Methods: 45 healthy male SD rats were fed with normal diet for one week, and were divided into 3 groups randomly, i.e. ACTH1-24 group (n=15), ACTH4-10 group (n=15) and control group (n=15). ACTH1-24 group received a subcutaneous injection of ACTHl-24 at a dose of 100μg/(kg·d) (dissolved in 1ml saline solution) for five consecutive days. ACTH4-10 group received a subcutaneous injection of ACTH4-10 at a dose of 300μg/(kg·d) (about 5 times molar concentration compared with ACTH1-24 group, dissolved in 1ml saline solution) for five consecutive days. Control group received the same volume of saline solution daily for five consecutive days. Then we drew blood to detect and compare the change of rats'serum lipid levels and renal function at pre-experiment and the fifth day of the experiment, respectively. After drew blood at the fifth day of the experiment ,we takes the liver tissue in anesthesia.Then, we detected the ApoM mRNA, ApoB mRNA, ApoA - I mRNA and LDL - R mRNA expression by Real-time RT - PCR spectrometry.Results: ACTH1-24 group: compared with pre-experiment, five days after ACTH1-24 injection, serum TC,TG, HDL and LDL levels were reduced about 7.9%,60.0%,0.6% and 25.6% respectively, and the differences of LDL ,TC and TG are significant (P<0.05,0.05,0.0001). Blood urea nitrogen level decreased 14.6% ( P<0.05). Serum Cr level increase about 21.1%, but no significant difference was found. Compared with the control group,the ApoM mRNA, ApoB mRNA, ApoA - I mRNA and LDL - R mRNA expression have increased , and the liver LDL-R mRNA expression increased about4.6 times, and the difference is significant (P<0.05);ACTH4-10 group: five days after ACTH4-10 injection, serum LDL levels were reduced about 17.3%, and the difference of LDL is significant (P<0.05), but no significant differences were found of the rest;there was no difference about renal function in rats.Compared with the control group,the liver LDL-R mRNA expression increased about 12 times, and the difference is significant (P<0.05), but no significant difference were found about the ApoM mRNA, ApoB mRNA and ApoA - I mRNA expression .Conclusions: The SD rat model is suitable for the research on the mechanism of action of ACTH on lowering lipids; ACTH1-24 has the effect of lipid-lowering and improving renal function,and its lipid-lowering mechanism concerned with the LDL receptor ; ACTH4-10 may also has the effect of lipid-lowering and its lipid-lowering mechanism concerned with the LDL receptor, but there were no renal function improving effect. |
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