Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan City, Hubei Province, 430060, China.
Department of Gastroenterology, GuiZhou Provincial People's Hospital, Guiyang City, Guizhou Province, 550002, China.
Curr Mol Med. 2023;23(9):971-980. doi: 10.2174/1566524023666220908112922.
Acute acalculous cholecystitis (AAC) is characterized by acute onset, rapid progression, high mortality, and various complications. Cyclophilin D (CypD) regulates the mitochondrial permeability transition pore (MPTP) and is involved in the occurrence of ischemia-reperfusion injury and inflammation; however, the role of CypD in AAC remains unclear.
Guinea pigs of 300-350 g were randomly divided into three groups, namely the sham group, the common bile duct ligation-24h group (CBDL-24h group), and the CBDL-48h group. Western blot and qRT-PCR were applied to analyze the differential expression of CypD in each group, and transmission electron microscopy was employed to detect changes in mitochondrial structure. Inhibiting the activity of CypD by Cyclosporine A (CsA), we evaluated the difference of mitochondrial utilizing mitochondrial swelling, reactive oxygen species (ROS) detection and mitochondrial membrane potential.
Compared with the sham group, the prolongation of obstruction aggravated gallbladder inflammation and upregulated CypD expression in the CBDL-24h and CBDL-48h groups. The degree of mitochondrial swelling was increased, and the opening of MPTP was prolonged in the CBDL-24h and 48h groups. Decreasing the expression of CypD could repress the opening of MPTP, prevent manipulation of the mitochondrial membrane potential, and ultimately diminish the levels of intracellular ROS and apoptosis.
CypD plays a proinflammatory role in the development of AAC by regulating the opening of MPTP. Inhibiting the activity of CypD could reduce the levels of ROS and apoptosis, rescue the function of mitochondria and finally alleviate AAC. Therefore, CypD might serve as a potential therapeutic target for ACC.
急性非结石性胆囊炎（AAC）以起病急、进展快、死亡率高、并发症多为特点。亲环素 D（CypD）调节线粒体通透性转换孔（MPTP），并参与缺血再灌注损伤和炎症的发生；然而，CypD 在 AAC 中的作用尚不清楚。
300-350g 豚鼠随机分为三组，即假手术组、胆总管结扎 24h 组（CBDL-24h 组）和胆总管结扎 48h 组。采用 Western blot 和 qRT-PCR 分析各组 CypD 的差异表达，透射电镜观察线粒体结构变化。用环孢素 A（CsA）抑制 CypD 的活性，通过线粒体肿胀、活性氧（ROS）检测和线粒体膜电位来评估线粒体利用的差异。
与假手术组相比，梗阻时间延长加重胆囊炎症，CypD 在 CBDL-24h 和 CBDL-48h 组表达上调。CBDL-24h 和 48h 组线粒体肿胀程度增加，MPTP 开放时间延长。降低 CypD 的表达可以抑制 MPTP 的开放，防止线粒体膜电位的改变，最终降低细胞内 ROS 和凋亡水平。
CypD 通过调节 MPTP 的开放在 AAC 的发展中发挥促炎作用。抑制 CypD 的活性可以降低 ROS 和凋亡水平，挽救线粒体功能，最终缓解 AAC。因此，CypD 可能成为 ACC 的潜在治疗靶点。
