基因重组生长激素对肾病大鼠脂代谢的影响及其机制的研究

Experimental Study on Effects and Mechanism of Recombinant Human Growth Hormone on Serum Lipid in Nephrotic Rats

目的观察基因重组生长激素(recombinant human growth hormone,rhGH)对肾病综合征大鼠血脂水平的影响并探讨其机制。方法制备阿霉素肾病大鼠模型,设正常对照组(A组,6只)、肾病组(B组,12只)和rhGH治疗组(C组,12只),全自动生化仪测量血清TC、TG、HDL和LDL,以流式细胞仪测量肝细胞GHR的表达,放射免疫法测血清IGF-1水平。结果(1)B组和C组大鼠TC、TG、LDL明显高于A组(P<0.05),C2组与B2组相比TC、TG、LDL显著降低(P<0.05),C1组HDL水平与B1组相比显著升高(P<0.05)。(2)B组和C1组大鼠血清IGF-1浓度显著低于A组,C2组IGF-1水平与A组相比无统计学差异;(3)B组和C组肝脏GHR较A组显著降低(P<0.001),C2组比B2组肝脏GHR表达明显增加(P<0.01)。结论肝细胞GHR表达下降参与了NS大鼠高脂血症的发生,rhGH通过提高肝细胞GHR的表达而调节血脂的水平。

Objective To investigate the effects of recombinant human growth hormone （rhGH） on serum TC,TG,HDL and LDL in nephrotic rats. Methods Thirty male Spraque - Dawley （SD） rats were randomly divided into control group （A group,n = 6）, doxorubi- ncin - induced nephrotic griyo （ B groups,n = 12） and rhGH - treated nephrotic group（ C groups,n = 12）. IGF - 1 concentration in serum was measured with RIA. TC, TG, HDL and LDL level in serum were measured with automatic biochemistry appliance. GHR level in liver was detected by flow cytometry. Results （ 1 ） Serum TC, TG and LDL level of the B and C groups were all significantly higher than those of the A group and these indicators in C2 group were decreasd as compared with B2 group. Serum HDL level was increased significantly in C1 group as compared with BI group. （2） IGF - 1 concentration in serum was decreased in B and C1 groups as compared with A group. No significant difference was observed between C2 group and A group on serum IGF - 1. （3） Hepatic GHR expression were significantly decreased in both B and C groups as compared with A group and increased in C2 group compared with B2 group. Conclusion The dyslipidemia in nephrotic rats might be caused by the decreased expression of hepatic GHR. rhGH could improve the serum lipid by promoting the expression of hepatic GHR.