Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Mol Med Rep. 2020 Mar;21(3):1633-1639. doi: 10.3892/mmr.2020.10961. Epub 2020 Jan 24.
The present study aimed to clarify the protective effects of p‑methoxyphenyl morpholino‑phosphinodithioic acid (GYY4137), a water‑soluble hydrogen sulfide‑releasing molecule, on a rat model of intestinal ischemia‑reperfusion (IIR). A total of 40 healthy male Sprague Dawley (SD) rats were randomly divided into four groups (n=10/group): Group A, a sham‑surgery group; Group B, the IIR group; group C, rats with IIR that were administered an abdominal injection of low‑dose GYY4137 (40 mg/kg); and group D, rats with IIR that were administered high‑dose GYY4137 (80 mg/kg). Intestinal histomorphology was observed using hematoxylin and eosin staining, and the concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured. Apoptotic index (AI) was determined by terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling. Reverse transcription‑quantitative PCR analysis was performed to assess the expression levels of intestinal caspase‑3, Bax and Bcl‑2. Notably, disordered arrangement of intestinal villi and mucosal necrosis were detected in group B, which was substantially improved by GYY4137 treatment (groups C and D). MDA content (nmol/mg) was 2.83±0.36, 9.23±0.78, 4.97±0.45 and 3.51±1.05 nmol/mg in groups A, B, C and D, respectively. In addition, SOD concentration (U/mg) was 135.37±3.34, 76.45±1.39, 95.13±1.64 and 115.13±2.54 in groups A, B, C and D, respectively. Furthermore, AI in group B (21.73±1.17%) was markedly higher than that in group A (4.53±0.28%) and in the GYY4137 intervention groups (9.53±0.96 and 6.53±0.76% in groups C and D, respectively). Compared with in group A, the mRNA expression levels of Bax and caspase‑3 were markedly higher in group B (P<0.05), whereas the expression of Bcl‑2 was significantly lower (P<0.05). Furthermore, compared with in group B, Bcl‑2 expression was higher, and Bax and caspase‑3 expression was lower in groups C and D (P<0.05). In conclusion, GYY4137 may alleviate IIR‑induced damage in SD rats.
本研究旨在阐明水溶性硫化氢供体 p-甲氧基苯吗啉-膦酸二硫代酸(GYY4137)对大鼠肠缺血再灌注(IIR)模型的保护作用。将 40 只健康雄性 Sprague Dawley(SD)大鼠随机分为四组(每组 10 只):A 组,假手术组;B 组,IIR 组;C 组,接受低剂量 GYY4137(40mg/kg)腹腔注射的 IIR 大鼠;D 组,接受高剂量 GYY4137(80mg/kg)腹腔注射的 IIR 大鼠。采用苏木精-伊红(HE)染色观察肠道组织形态学变化,测定丙二醛(MDA)和超氧化物歧化酶(SOD)浓度。采用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法(TUNEL)检测细胞凋亡指数(AI)。采用逆转录-定量聚合酶链反应(qRT-PCR)分析评估肠道 caspase-3、Bax 和 Bcl-2 的表达水平。结果显示,B 组肠绒毛排列紊乱,黏膜坏死,GYY4137 治疗(C 组和 D 组)显著改善了上述变化。各组 MDA 含量(nmol/mg)分别为:A 组 2.83±0.36、B 组 9.23±0.78、C 组 4.97±0.45、D 组 3.51±1.05;各组 SOD 浓度(U/mg)分别为:A 组 135.37±3.34、B 组 76.45±1.39、C 组 95.13±1.64、D 组 115.13±2.54。此外,B 组 AI(21.73±1.17%)明显高于 A 组(4.53±0.28%)和 GYY4137 干预组(C 组和 D 组分别为 9.53±0.96%和 6.53±0.76%)。与 A 组相比,B 组 Bax 和 caspase-3 的 mRNA 表达水平明显升高(P<0.05),而 Bcl-2 的表达水平明显降低(P<0.05)。此外,与 B 组相比,C 组和 D 组 Bcl-2 表达水平升高,Bax 和 caspase-3 表达水平降低(P<0.05)。综上所述,GYY4137 可能减轻 SD 大鼠 IIR 引起的损伤。