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目的:探讨硫化氢(H2S)对去卵巢骨质疏松(OP)大鼠骨组织中自噬相关基因Beclin-1和LC3-Ⅱ表达的影响,以阐明其抗OP的分子机制。方法:30只健康SD雌性大鼠随机分为对照组、去卵巢模型组和外源性H2S供体硫氢化钠(Na HS)(50μmol/kg)组,12周后检测血雌二醇(E2)和H2S、血清钙、血清磷、血碱性磷酸酶(ALP)及尿钙和尿脱氧吡啶啉(Dpd)水平。采用Micro-CT测量大鼠胫骨的骨密度(BMD),采用Western Blot检测胫骨中自噬相关蛋白Beclin-1和LC3-Ⅱ的表达。结果:与对照组比较,去卵巢模型组大鼠血清E2和H2S水平及胫骨的BMD均显著性降低,尿Dpd、尿钙、ALP、血清磷和钙的水平均显著增加,Beclin-1和LC3-Ⅱ的表达均显著增加,差异均有统计学意义(均P<0.05)。与去卵巢模型组比较,Na HS组大鼠血清H2S水平和胫骨的BMD显著增加,尿钙、尿Dpd、血清钙、血清磷和ALP水平显著降低,Beclin-1和LC3-Ⅱ的表达均显著降低,差异均有统计学意义(P<0.05)。结论:内源性H2S的减少参与了去卵巢后OP的发生,外源性H2S抑制了去卵巢所导致的OP,其机制可能与H2S抑制骨骼中的自噬有关。
AIM: To investigate the effect of hydrogen sulfide (H2S) on the expression of autophagy-related genes Beclin-1 and LC3-Ⅱ in ovariectomized rats with osteoporosis (OP) to clarify the molecular mechanism of anti-OP. Methods: Thirty healthy female Sprague-Dawley rats were randomly divided into control group, ovariectomized group and exogenous H2S donor sodium hydrosulphide (Na HS) group (50 μmol / kg). After 12 weeks, serum estradiol ) And H2S, serum calcium, serum phosphorus, blood alkaline phosphatase (ALP) and urinary calcium and urine deoxypyridinoline (Dpd) levels. The bone mineral density (BMD) of the tibia was measured by Micro-CT. The expression of autophagy-related proteins Beclin-1 and LC3-Ⅱ in the tibia was detected by Western Blot. Results: Compared with the control group, the levels of serum E2 and H2S and the BMD of tibia in ovariectomized rats were significantly decreased, while the levels of urinary Dpd, urinary calcium, ALP, serum phosphorus and calcium were significantly increased. Beclin-1 and LC3 -II expression were significantly increased, the differences were statistically significant (P <0.05). Compared with the ovariectomized model group, the levels of serum H2S and the tibial BMD of rats in Na HS group were significantly increased, urinary calcium and urine Dpd, serum calcium, serum phosphorus and ALP levels were significantly decreased, Beclin-1 and LC3-Ⅱ expression were significantly Reduce, the difference was statistically significant (P <0.05). CONCLUSION: The decrease of endogenous H2S is involved in the development of OP after ovariectomy. Exogenous H2S inhibits ovariectomized OP, which may be related to the inhibition of H2S on autophagy in bone.