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复杂性肾结石术后感染相关危险因素分析及与miRNA-145、miRNA-218和PI3K/Akt蛋白通路表达的关系
马飞跃
丁春珊
作者及单位信息
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DOI: 10.3760/cma.j.cn341190-20240730-00976
Analysis of risk factors for infection after surgery for complex kidney stones and their correlation with the expressions of miRNA-145 and miRNA-218 as well as and the PI3K/Akt signaling pathway
Ma Feiyue
Ding Chunshan
Authors Info & Affiliations
Ma Feiyue
Department of Urology, Ningbo Fourth Hospital, Ningbo 315700, Zhejiang Province, China
Ding Chunshan
Department of Urology, Ningbo Fourth Hospital, Ningbo 315700, Zhejiang Province, China
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DOI: 10.3760/cma.j.cn341190-20240730-00976
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摘要

目的分析复杂性肾结石术后感染的相关危险因素及其与微小RNA(miRNA)-451、miRNA-218表达及磷脂酰肌醇-3(PI3K)/蛋白激酶B信号作用通道(Akt)蛋白通路表达的关系。

方法选取宁波市第四医院于2021年3月至2024年3月收治的复杂性结石患者213例为研究对象,均行经皮肾镜碎石取石术(PCNL),记录患者术后感染发生情况。采用实时荧光定量PCR法(qRT-PCR)测定血清miRNA-145和miRNA-218表达;采用Western Blot法测定PI3K和Akt蛋白表达。多因素logistic回归分析复杂性肾结石术后感染危险因素;比较复杂性肾结石术后感染组与无感染组血清miRNA-145和miRNA-218表达、PI3K和Akt蛋白灰度值;Pearson分析miRNA-145、miRNA-218、PI3K和Akt表达与术后感染相关性。

结果复杂性结石患者213例中,PCNL术后发生感染患者46例,占21.60%;未发生感染患者167例,占78.40%。两组性别、年龄、合并高血压、合并冠心病和吸烟史比较,差异无统计学意义( P > 0.05);感染组结石直径 ≥ 3 cm占比[78.26%(36/46)]高于无感染组[47.31%(79/167)],合并糖尿病占比[30.43%(14/46)]高于无感染组[10.79%(18/167)],中重度肾积水占比[89.13%(41/46)]高于无感染组[68.86%(115/167)],手术时间 ≥ 60 min占比[86.96%(40/46)]高于无感染组[61.68%(103/167)],术后留置导尿管 ≥ 7 d占比[69.57%(32/46)]高于无感染组[23.95%(40/167)]( χ 2=13.91、10.91、7.55、10.44、33.53,均 P < 0.05)。结石直径 ≥ 3 cm、合并糖尿病、中重度肾积水、手术时间 ≥ 60 min及术后留置导尿管 ≥ 7 d等为影响复杂性肾结石术后感染独立危险因素( OR=7.192、4.870、5.089、12.988、9.007)。感染组血清miRNA-145相对表达量(1.37±0.38)和miRNA-218相对表达量(0.76±0.21),均低于无感染组的(2.86±0.62)和(1.97±0.38)( t=15.50、20.71,均 P < 0.001)。感染组PI3K蛋白表达灰度值(1.23±0.31)和Akt蛋白表达灰度值(0.98±0.23),均高于无感染组的(0.68±0.20)和(0.42±0.12)( t=14.49、22.36,均 P < 0.001)。采用Pearson分析miRNA-145、miRNA-218与术后感染呈负相关,PI3K和Akt表达与术后感染呈正相关( r=-0.57、-0.48、0.62、0.59,均 P < 0.001)。

结论复杂性肾结石术后感染受多因素影响,其中结石直径、合并糖尿病、肾积水程度、手术时间和术后留置导尿管时间为其独立危险因素;且术后感染患者miRNA-145和miRNA-218低表达,而PI3K和Akt蛋白高表达。

肾结石;碎石术;泌尿道感染;危险因素;微RNAs;磷酸肌醇3-激酶;蛋白激酶类
ABSTRACT

ObjectiveTo analyze the risk factors for infection after surgery for complex kidney stones and to investigate their correlation with the expressions of microRNA (miRNA)-451 and miRNA-218, as well as the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway.

MethodsA total of 213 patients with complex kidney stones who were admitted to Ningbo Fourth Hospital from March 2021 to March 2024 were included in this study. All patients underwent percutaneous nephrolithotomy (PCNL), and the occurrence of postoperative infections was recorded. The expression levels of serum miRNA-145 and miRNA-218 were measured using quantitative real-time PCR (qRT-PCR), while the expression of PI3K and Akt proteins was determined using Western blot assay. Multivariate logistic regression was performed to analyze the risk factors associated with infection after surgery for complex kidney stones. The expression levels of serum miRNA-145 and miRNA-218, as well as the grayscale values of PI3K and Akt proteins, were compared between the infection and non-infection groups. Pearson correlation analysis was conducted to assess the correlation between the expression of miRNA-145, miRNA-218, PI3K, and Akt and the occurrence of postoperative infections.

ResultsAmong the 213 patients with complex kidney stones, 46 (21.60%) developed infections after PCNL, while 167 (78.40%) did not. There were no statistically significant differences between the two groups in terms of sex, age, history of hypertension, history of coronary heart disease, and history of smoking (all P > 0.05). The proportion of patients in the infection group with stone diameters ≥ 3 cm was higher than that in the non-infection group [78.26% (36/46) vs. 47.31% (79/167)]. The proportion of patients with diabetes in the infection group was higher than that in the non-infection group [30.43% (14/46) vs. 10.79% (18/167)]. Moreover, the incidence of moderate to severe hydronephrosis in the infection group was higher than that in the non-infection group [ 89.13% (41/46) vs. 68.86% (115/167)]. The proportion of patients with a surgical duration of ≥ 60 minutes in the infection group was higher than that in the non-infection group [86.96% (40/46) vs. 61.68% (103/167)]. Additionally, the proportion of patients in the infection group with a duration of postoperative urinary catheterization of ≥ 7 days was significantly higher than that in the non-infection group [69.57% (32/46) vs. 23.95% (40/167)]. The differences in stone diameter ≥ 3 cm, presence of diabetes, moderate to severe hydronephrosis, surgical duration ≥ 60 minutes, and postoperative urinary catheterization duration ≥ 7 days between the two groups were statistically significant ( χ² = 13.91, 10.91, 7.55, 10.44, 33.53, all P < 0.05). Factors such as stone diameter ≥ 3 cm, presence of diabetes, moderate to severe hydronephrosis, surgical duration ≥ 60 minutes, and postoperative urinary catheterization duration ≥ 7 days were identified as independent risk factors for infection after surgery for complex kidney stones ( OR = 7.192, 4.870, 5.089, 12.988, 9.007). In the infection group, the relative expression levels of serum miRNA-145 and miRNA-218 were (1.37 ± 0.38) and (0.76 ± 0.21), respectively, which were significantly lower than those in the non-infection group [(2.86 ± 0.62), (1.97 ± 0.38), t = 15.50, 20.71, both P < 0.001]. In the infection group, the grayscale values of PI3K protein expression and Akt protein expression were (1.23 ± 0.31) and (0.98 ± 0.23), respectively, which were significantly higher than those in the non-infection group [(0.68 ± 0.20), (0.42 ± 0.12), t = 14.49, 22.36, both P < 0.001]. Pearson correlation analysis revealed that the expressions of miRNA-145 and miRNA-218 were negatively correlated with postoperative infections, while the expressions of PI3K and Akt were positively correlated with postoperative infection ( r = -0.57, -0.48, 0.62, 0.59, all P < 0.001).

ConclusionsPostoperative infection in complex kidney stones is influenced by multiple factors, among which stone diameter, presence of diabetes, degree of hydronephrosis, surgical duration, and duration of postoperative urinary catheterization are independent risk factors. Additionally, patients with postoperative infection exhibit low expression levels of miRNA-145 and miRNA-218, while PI3K and Akt proteins show high expression levels.

Kidney calculi;Lithotripsy;Urinary tract infections;Risk factors;MicroRNAs;Phosphatidylinositol 3-kinase;Protein kinases
Ma Feiyue, Email: mocdef.qabq99148716
引用本文

马飞跃,丁春珊. 复杂性肾结石术后感染相关危险因素分析及与miRNA-145、miRNA-218和PI3K/Akt蛋白通路表达的关系[J]. 中国基层医药,2025,32(03):426-431.

DOI:10.3760/cma.j.cn341190-20240730-00976

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复杂性肾结石包括孤立肾结石、马蹄肾结石、鹿角形结石及肾多发结石等,常伴肾脏结构异常,并且给治疗造成较大难度,一直是泌尿外科研究热点 1 , 2。目前,外科手术是复杂性肾结石首选治疗方法,不仅可取得良好疗效,并且可解除梗阻及有效清除结石 3。但术后感染仍为复杂性结石术后主要并发症之一,不仅影响治疗效果,并且可能引发败血症等 4 , 5。因此,及时明确复杂性肾结石术后感染危险因素,对降低术后感染发生具有重要临床研究价值 6。微小RNA(miRNA)参与多种复杂生物学过程。目前,关于miRNA与复杂性肾结石方面研究甚少。磷脂酰肌醇-3(PI3K)/蛋白激酶B信号作用通道(Akt)蛋白通路参与炎症反应过程,可调节炎症因子表达,而术后感染患者会发生明显炎症反应。因此,本研究选自宁波市第四医院于2021年3月至2024年3月收治的复杂性结石患者213例,探讨复杂性肾结石术后感染危险因素与miRNA-451和miRNA-218表达及PI3K/Akt蛋白通路的关系。
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备注信息
A
马飞跃,Email: mocdef.qabq99148716
B

马飞跃:试验设计、采集数据、起草文章;丁春珊:统计分析、技术支持

C
马飞跃, 丁春珊. 复杂性肾结石术后感染相关危险因素分析及与miRNA-145、miRNA-218和PI3K/Akt蛋白通路表达的关系[J]. 中国基层医药,2025,32(3):426-431. DOI:10.3760/cma.j.cn341190-20240730-00976.
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