Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People's Republic of China.
Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, 150001, People's Republic of China.
Drug Des Devel Ther. 2021 Mar 3;15:973-981. doi: 10.2147/DDDT.S280322. eCollection 2021.
The formation of hypertrophic scars (HS) can result in the failure of glaucoma surgery, and fibrosis is known to be closely associated with the progression of HS. Dihydroartemisinin (DHA) has been reported to inhibit the progression of fibrosis; however, whether DHA can alleviate the formation of HS remains unclear.
In the present study, in order to examine the effects of DHA on the progression of HS, human Tenon's capsule fibroblasts (HTFs) were isolated from patients who underwent glaucoma surgery. In addition, Western blot analysis, microtubule associated protein 1 light chain 3 α staining and reverse transcription-quantitative PCR were performed to detect protein and mRNA expression levels in the HTFs, respectively. Cell proliferation was detected by Ki67 staining. Flow cytometry was used to examine apoptosis and reactive oxygen species (ROS) levels in the HTFs.
The results revealed that TGF-β promoted the proliferation and fibrosis of HTFs; however, DHA significantly reversed the effects of TGF-β by increasing cell autophagy. In addition, DHA notably induced the apoptosis of TGF-β-stimulated HTFs by increasing the ROS levels, while these increases were partially reversed by 3-methyladenine. Furthermore, DHA notably increased the expression of microRNA (miR)-145-5p in HTFs in a dose-dependent manner.
The present study demonstrated that DHA inhibits the TGF-β-induced fibrosis of HTFs by inducing autophagy. These findings may aid in the development of novel agents for the prevention of the formation of HS following glaucoma surgery.
增生性瘢痕（HS）的形成可导致青光眼手术失败，纤维化与 HS 的进展密切相关。二氢青蒿素（DHA）已被报道可抑制纤维化的进展；然而，DHA 是否能减轻 HS 的形成尚不清楚。
在本研究中，为了研究 DHA 对 HS 进展的影响，从接受青光眼手术的患者中分离出人 Tenon 囊成纤维细胞（HTFs）。此外，通过 Western blot 分析、微管相关蛋白 1 轻链 3α 染色和逆转录定量 PCR 分别检测 HTFs 中的蛋白和 mRNA 表达水平。通过 Ki67 染色检测细胞增殖。通过流式细胞术检测 HTFs 中的细胞凋亡和活性氧（ROS）水平。
结果表明，TGF-β促进 HTFs 的增殖和纤维化；然而，DHA 通过增加细胞自噬显著逆转了 TGF-β的作用。此外，DHA 通过增加 ROS 水平显著诱导 TGF-β 刺激的 HTFs 凋亡，而 3-甲基腺嘌呤部分逆转了这些增加。此外，DHA 显著地以剂量依赖的方式增加 HTFs 中 microRNA（miR）-145-5p 的表达。
本研究表明，DHA 通过诱导自噬抑制 TGF-β 诱导的 HTFs 纤维化。这些发现可能有助于开发预防青光眼手术后 HS 形成的新型药物。
