丁酸钠器官毒性研究

Sodium Butyrate Toxicity Studies

目的:研究组蛋白去乙酰化酶抑制剂(histone deacetylase inhibition HDACi):丁酸钠(Sodium Butyrate Na B)腹腔连续给药对BALB/C小鼠体重增长及器官发育的影响。方法:20只健康,3周BALB/C小鼠随机分成2组(丁酸钠组和对照组);丁酸钠组腹腔注射丁酸钠(Na B)1.2 g/Kg·d,连续21天;对照组同时间腹腔注射等量生理盐水。21天后,测量体重;行4%多聚甲醛灌注、固定,取心脏,肝脏,脾脏,肺脏,肾脏,脑组织以及小肠组织器官,做石蜡切片,HE染色两组比较有无器官损害。结果:1.丁酸钠组与对照组比较,两组动物体重增长良好,平均增长11 g,两组间无统计学差异(P>0.05)。2.HE染色见丁酸钠组:心肌细胞无变性,坏死,无炎性细胞浸润,无肉芽组织形成;脾脏红、白髓结构清晰,脾窦无扩张,未见炎性细胞浸润;肺间质无扩张,充血,未见纤维化,肺泡无水肿;肾小管上皮细胞无变性坏死,肾间质未见水肿;脑细胞周围间隙和小血管间隙无增宽;肠道纤毛上皮排列整齐,肠壁无出血,坏死,无渗出;肝细胞围绕中央静脉呈放射状排列,细胞无水肿,无胆汁淤积。未发现上述器官的病理变化。结论:丁酸钠长期腹腔给药安全,无明显毒副作用。

Objective： Research the organ toxicity of Histone deacetylase inhibition（HDACi）; Sodium Butyrate（ Na B） through the continuous iintraperitoneal injection in BALB/C mice. Methods： Twenty healthy, 3W BALB/C mice were randomly divided into 2groups（Na B group and the control group）, Intraperitoneal injection of Na B 1.2 g/Kg·d for 21 days（Na B group）; intraperitoneal injection of equivalent physiological saline for 21 days to be the control group. After measuring the weight gain, 4 % paraformaldehyde glutaraldehyde perfusion fixation, do the HE test of heart, liver, spleen, lung, kidney, brain tissue and intestinal tissue pathological slices. Results： 1.Na B group compared with the control group, average growth in 11 g. There is no statistical difference between the two groups（P〉0.05）.2. The organ HE staining of Na B group. Cardiac muscle cell have no degeneration, necrosis, or inflammatory cell infiltration, and granulation tissue formation; Spleen＇s red and white pulp structure is clear, there is no expansion of splenic sinus, and inflammatory cell infiltration; Pulmonary interstitial have no expansion, congestion, or fibrosis, and no alveolar edema; Renal tubular epithelial cells have no degeneration necrosis, renal interstitial have no edema. Brain cell＇s peripheral clearance and small vessel have no broaden; Intestinal ciliated epithelium neatly, intestinal wall without hemorrhage, necrosis, and leakage. liver cells lie in a radial pattern around the central vein,without edema or cholestasis. Did not observe any pathological changes on the above organ. Conclusions： Sodium butyrate intraperitoneal injection is safe for a long time, and have no obvious side effects.