Diarrhea‐predominant irritable bowel syndrome (IBS‐D) is one of the most common gastrointestinal disorders in the world, lacking effective therapies. The crucial roles of microRNAs (miRNAs) in IBS‐D have attracted increasing attention. The aim of this study is to investigate the effects of miR‐495 on the visceral sensitivity of the IBS‐D through the PI3K/AKT signaling pathway by targeting PKIB. Microarray data analysis was employed to screen the differentially expressed genes related to IBS‐D and regulatory miRNAs. Then, mice were perfused with acetic acid into the rectum to establish the IBS‐D model. Next, PKIB expression was measured in IBS‐D mice. Additionally, model mice were injected with a series of adenovirus vector to investigate the influence of miR‐495 on visceral sensitivity and rectal function in IBS‐D mice with the involvement of PKIB and PI3K/AKT signaling pathway. The IBS‐D mouse model was successfully established. PKIB was the target gene of miR‐495, and highly expressed in mice with IBS‐D. Silencing PKIB reduced visceral sensitivity in mice with IBS‐D, and overexpression of miR‐495 decreased visceral sensitivity in mice with IBS‐D by inhibiting PKIB. Moreover, miR‐495 upregulation inhibited PI3K/AKT signaling pathway through downregulating PKIB. To sum up, this study reveals that miR‐495 upregulation can reduce visceral sensitivity in IBS‐D via inhibition of PI3K/AKT signaling pathway by targeting PKIB. It suggests that miR‐495 presents a potential target for IBS‐D therapy.

中文翻译：

---

microRNA-495 通过 PKIB 抑制 PI3K/AKT 信号通路降低腹泻型肠易激综合征小鼠的内脏敏感性

腹泻型肠易激综合征（IBS-D）是世界上最常见的胃肠道疾病之一，缺乏有效的治疗方法。微小RNA（miRNA）在IBS-D中的关键作用引起了越来越多的关注。本研究的目的是通过靶向 PKIB 研究 miR-495 通过 PI3K/AKT 信号通路对 IBS-D 内脏敏感性的影响。采用微阵列数据分析筛选与 IBS-D 和调节 miRNA 相关的差异表达基因。然后，将乙酸灌入小鼠直肠以建立IBS-D模型。接下来，在 IBS-D 小鼠中测量 PKIB 表达。此外，为模型小鼠注射一系列腺病毒载体，研究 miR-495 对 IBS-D 小鼠内脏敏感性和直肠功能的影响，涉及 PKIB 和 PI3K/AKT 信号通路。成功建立IBS-D小鼠模型。PKIB 是 miR-495 的靶基因，在 IBS-D 小鼠中高表达。沉默 PKIB 降低了 IBS-D 小鼠的内脏敏感性，miR-495 的过表达通过抑制 PKIB 降低了 IBS-D 小鼠的内脏敏感性。此外，miR-495 上调通过下调 PKIB 来抑制 PI3K/AKT 信号通路。综上所述，本研究表明，miR-495 上调可以通过靶向 PKIB 抑制 PI3K/AKT 信号通路来降低 IBS-D 的内脏敏感性。这表明 miR-495 是 IBS-D 治疗的潜在靶点。