SUMMARY Since the 1980 s nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), the endogenous gas molecules produced from metabolic pathway, have been realized as signal molecules to be involved in the regulation of body homeostasis and to play important roles under physiological and pathophysiological conditions. The researches on these endogenous gas signal molecules opened a new avenue in life science. To explore the new member of gasotransmitter family, other endogenous gas molecules which have been regarded as metabolic waste up to date, and their biological regulatory effects have been paid close attention to in the current fields of life science and medicine. Sulfur dioxide (SO2) can be produced endogenously from normal metabolism of sulfur-containing amino acids. L-cysteine is oxidized via cysteine dioxygenase to L-cysteinesulfinate, and the latter can proceed through transamination by glutamate oxaloacetate transaminase (GOT) to β-sulfinylpyruvate which decomposes spontaneously to pyruvate and SO2. In mammals, activated neutrophils by oxidative stress can convert H2S to sulfite through a reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-dependent process. The authors detected endogenous production of SO2 in all cardiovascular tissues, including in heart, aorta, pulmonary artery, mesenteric artery, renal artery, tail artery and the plasma SO2 content. As the key enzyme producing SO2, GOT mRNA in cardiovascular system was detected and found to be located enrichedly in endothelial cells and vascular smooth muscle cells near the endothelial layer.When the normal rats were treated with hydroxamate(HDX), a GOT inhibitor, at a dose of 3.7 mg/kg body weight, the blood pressure (BP) went high markedly, the ratio of wall thickness to lumen radius was increased by 18.34%, and smooth muscle cell proliferation was enhanced. The plasma SO2 level in the rats injected with 125 μmol/kg body weight SO2 donor was increased to 721.98±30.11 μmol/L at the end of 30 seconds, while th
目的 探讨新型气体信号分子二氧化硫（SO2）对自发性高血压大鼠（SHR）主动脉平滑肌细胞增殖与凋亡的调节作用。方法 4周龄SHR大鼠随机分为SHR对照组、Na2SO3／NaHSO3组（外源性SO2供体组），每组8只。4周龄正常血压WistarKyoto（WKY）大鼠8只作为正常对照（WKY对照组）。5周后检测大鼠血压及主动脉形态学指标，以高效液相色谱（HPLC）法测定血浆SO2水平；采用原位缺口末端标记方法（TUNEL）检测大鼠主动脉平滑肌细胞凋亡；采用免疫组织化学方法检测主动脉平滑肌细胞增殖细胞核抗原（PCNA）及凋亡相关蛋白Bcl-2、Fas和半胱氨酸蛋白水解酶（caspase）-3的表达，并进行图像分析。结果 5周后SHR对照组血压、血管壁厚与内径比均明显高于WKY对照组[（172±10）nl／nHgV8（112±9）nl／nHg、0．073±0．004V80．057±0．004，均P〈0．01，1mm Hg=0．133kPa]，血浆SO2水平显著低于WKY对照组[（6．4±1．5）μmol／LV8（11．3±1．0）μmol／L]，主动脉平滑肌细胞增殖指数高（0．32±0．06 vs 0．05±0．03），而凋亡指数小（0．16±0．07 vs 0．30±0．19），主动脉平滑肌细胞Bcl-2蛋白表达高（0．209±0．007 vs 0．202±0．006，P〈0．01），Fas、caspase-3蛋白表达弱（0．205±0．006 vs 0．211±0．005、0．229±0．005 vs 0．244±0．010，均P〈0．01）。外源性SO2供体组与SHR对照组比较，血压低[（128±7）mm Hg]，血管壁厚与内径比低（0．066±0．002），血浆SO2含量高[（8．3±1．0）μmol／L]，主动脉平滑肌细胞增殖指数低（0．14±0．03），凋亡指数高（0．40±0．11），主动脉平滑肌细Bcl-2蛋白表达低（0．199±0．006），Fas和caspase-3蛋白呈高表达（分别为0．218±0．003、0．251±0．011，均P〈0．01）。结论 SO2可抑制高血压大鼠主动脉血管平滑肌细胞增殖、促进其细胞凋亡。SO2促进细胞凋亡的途径可能与其对主动脉平滑肌细�
