Analysis in correlations among serological indexes, differentiated syndrome of traditional Chinese medicine and severity of illness in ulcerative colitis
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摘要:目的 分析溃疡性结肠炎（UC）患者血清学指标[血红素加氧酶-1（HO-1）、外周血红细胞沉降率（ESR）和C反应蛋白（CRP）]、疾病严重程度及中医证型间的相关性。方法 将被诊断为UC的患者纳入实验组，将同期体检中心的26例健康体检人员纳入对照组，采集2组的血清样本。根据改良Mayo评分分级及肠镜检查结果评分分级标准，将UC患者分为轻、中、重度；根据中医辨证并结合临床实际，将其分为大肠湿热证、脾肾两虚证2种证型。空腹抽取肘静脉血，采用酶联免疫吸附法（ELISA）检测HO-1水平。记录UC患者就诊时外周ESR和CRP水平。比较2组血清中HO-1的表达情况；观察UC患者血清中HO-1、CRP、ESR指标，病情严重程度分级及中医证型的相关性。结果 实验组血清中HO-1表达水平高于对照组，差异有统计学意义（P < 0.01）。改良Mayo评分分级及肠镜结果评分分级为中、重度的患者HO-1、CRP和ESR水平高于轻度患者，重度患者高于中度患者，差异有统计学意义（P < 0.05）。大肠湿热证患者HO-1、CRP和ESR水平均高于脾肾两虚证，差异有统计学意义（P < 0.05）。大肠湿热证患者的肠镜及改良Mayo分级严重程度高于脾肾两虚证患者，差异有统计学意义（P < 0.05）。结论 HO-1、CRP和ESR水平与UC病情的严重程度相关。血液指标、肠镜检查结果评分以及改良Mayo评分不仅可作为衡量患者病情严重程度的参考标准，也可作为本病虚实和指导中医证型分型的依据。但HO-1在轻度UC中不敏感，因此在对UC初筛中的指导意义不大。Abstract:Objective To analyze the correlations among serological indexes[heme oxygenase-1(HO-1), erythrocyte sedimentation rate (ESR), and C reactive protein (CRP)], differentiated syndrome of traditional Chinese medicine and severity of illness in ulcerative colitis (UC).Methods A total of 26 patients diagnosed as UC were divided into experimental group, and 26 healthy subjects from the Physical Examination Center during the same period were included in control group. The plasma samples of the two groups were collected. Based on grading criteria of the modified Mayo Scale score and colonoscopy results score, the UC patients were classified into mild, moderate, and severe cases. According syndrome differentiation and clinical practice, they were differentiated as syndrome of dampness-heat in large intestine and deficiency of spleen and kidney syndrome. Elbow venous blood was extracted in a fasted state, and HO-1 level was tested with enzyme-linked immunosorbent assay (ELISA). CRP and ESR were recorded on admission. The expression of HO-1 in the serum of UC subjects and healthy subjects were compared. The relationships among the severity classification, the syndrome of TCM and blood indexes such as HO-1, CRP, and ESR were explored.Results The expression levels of HO-1 in the serum of UC subjects were higher than that of the healthy subjects(P < 0.01). Compared with the mild patients by grading of colonoscopic and modified Mayo scale scores, the levels of HO-1, CRP, and ESR in the plasma of the moderate and severe patients were significantly higher, and severe cases had higher indexes than the moderate ones (P < 0.05). HO-1, CRP and ESR levels in the plasma of syndrome of dampness-heat in large intestine were significantly higher than those of patients with deficiency of spleen and kidney syndrome (P < 0.05).Conclusion The levels of HO-1, CRP and ESR in plasma are correlated with the severity of UC. The plasma indexes, modified Mayo Scale score and colonoscopic scores can not only be utilized as reference standard to measure the severity of UC, but also as foundation of judge the deficiency and excess of the disease and TCM syndrome differentiation of UC. However, HO-1 plasma level is not sensitive in mild UC subjects, so it may not be helpful in screening the UC patients in the initial stage.
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1. 资料与方法
1.1 一般资料
本研究回顾性收集2019年2月—2021年2月接受腔内经皮肾镜碎石取石术及经尿道输尿管软镜碎石取石术治疗的190例肾结石患者的临床资料，并对其进行为期2年的术后随访。纳入标准: ①临床确诊为原发性肾结石且符合肾结石手术指征者; ②临床资料完整者; ③年龄≥18周岁者。排除标准: ①合并心、脑、肺等重要器官疾病者; ②中途失访者。所有手术均由同一位手术经验丰富的医师完成，对部分患者手术取出的结石进行成分分析。
收集患者的性别、年龄、BMI、吸烟史、饮酒史、结石数量、结石所在位置、结石成分以及是否患有高血压、糖尿病、高脂血症等基础疾病。所有患者在术后第3、6、12和24个月进行随访，内容包括肾功能、尿常规及影像学等检查，由临床医师根据超声波检查、尿路平片、CT检查结果明确患者是否为结石复发。
1.2 统计学分析
采用SPSS 25.0软件进行统计分析。符合正态分布的计量资料采用(均数±标准差)表示; 符合偏态分布的计量资料采用[M(P25, P75)]表示; 计数资料采用[n(%)]表示。采用单因素Logistic回归分析对纳入的因素进行分析比较，将差异有统计学意义的因素纳入后续的多因素Logistic回归分析。P＜0.05为差异有统计学意义。
2. 结果
2.1 一般资料比较
研究共纳入269例接受腔内手术治疗的肾结石患者，其中79例患者被剔除(45例患者手术治疗后未接受规律随访, 4例患者术后2年内死亡等)，其余190例患者纳入本研究，其中男115例，女75例; 年龄57.5(21.0, 93.0)岁; BMI 25.2(16.0, 44.0) kg/m2, BMI＜18.5 kg/m2 6例, BMI 18.5~25.0 kg/m2 93例, BMI>25.0~30.0 kg/m2 53例, BMI>30.0 kg/m2 38例; 高血压50例，糖尿病19例，高脂血症28例; 吸烟史35例，饮酒史19例; 结石位置右侧70例，左侧114例，双侧6例; 结石单发111例，结石多发79例。117例患者术后进行了结石分析，结果显示最常见的结石类型是碳酸钙类结石(57例)，其次是混合成分结石(39例)、尿酸类结石(11例)、碳酸磷灰类结石(6例)、磷酸铵镁类结石(2例)和胱氨酸类结石(2例)。术后2年随访结束时, 49例患者出现了结石复发，其中25例患者再次接受了手术治疗，其余患者选择继续随访观察。
2.2 单因素和多因素Logistic回归分析
单因素Logistic回归分析结果显示, BMI、糖尿病、吸烟、年龄和高血压是结石复发的影响因素。多因素Logistic回归分析结果显示，糖尿病和吸烟是结石复发的危险性因素，年龄和高血压是结石复发的保护性因素。此外，性别和饮酒对结石复发无明显影响，且结石特征(包括结石成分、位置和大小)与术后结石复发也无关，见表 1。
表 1 单因素和多因素Logistic回归分析结果因素 单因素Logistic回归分析 多因素Logistic回归分析 HR 95%CI P HR 95%CI P 男性 1.35 0.70~2.60 0.360 — — — 年龄 0.96 0.94~0.98 0.003 0.96 0.94~0.98 0.003 BMI＜18.5 kg/m2 1.45 0.20~8.20 0.660 — — — BMI>25.0 kg/m2 2.00 1.00~4.00 0.050 1.90 0.90~4.20 0.086 高血压 0.37 0.15~0.89 0.027 0.26 0.10~0.78 0.017 糖尿病 3.73 1.40~9.80 0.008 7.90 2.20~27.90 0.001 高脂血症 0.74 0.28~1.90 0.550 — — — 吸烟史 3.10 1.05~9.50 0.039 3.50 1.10~11.10 0.029 饮酒史 1.90 0.54~7.00 0.300 — — — 结石类型 草酸钙类 0.77 0.30~1.80 0.550 — — — 磷酸钙类 0.20 0.10~1.50 0.115 — — — 尿酸类 2.30 0.65~8.20 0.190 — — — 右侧结石 1.40 0.72~2.70 0.310 — — — 单发结石 0.96 0.82~1.12 0.587 — — — 3. 讨论
肾结石出现临床症状时往往给患者带来很大痛苦，尽管一些肾结石可以通过非手术方法自行排出，但仍有一部分患者需要接受手术治疗。肾结石手术治疗费用较高，尤其是微创腔内碎石治疗。因此，研究腔内手术治疗肾结石后结石复发的危险因素具有重要意义。研究[4-5]表明，初次结石发作后的5~10年内，泌尿系结石复发率为30%~50%。SONG S等[6]研究表明，泌尿系结石术后5年平均复发率为30%, 10年时为50%, 20年时达80%。
流行病学研究[7]认为，泌尿系结石的发生与代谢综合征的3种疾病相关: 肥胖、糖尿病和高血压。这些研究结果表明泌尿系结石是代谢综合征的后果，而不仅仅是一种独立的尿液成分异常导致的疾病[8]。本研究单因素Logistic回归分析显示，糖尿病和BMI>25.0 kg/m2是结石复发的危险性因素，高血压是预防结石复发的保护性因素。糖尿病和肾结石相互影响，糖尿病的早期诊断增大了肾结石发病的风险，同样肾结石也增加了糖尿病发病的风险[9]。肥胖和体质量增加是肾结石发病的独立危险因素[10]。肾结石似乎是高血压发展的危险因素，但是高血压是否与肾结石的形成相关尚不清楚[11-12]。很大一部分的高血压患者有更高的肾结石形成风险，尤其是当高血压伴有超重、摄入过多食盐及动物蛋白时。在高血压患者中，尿液中草酸和钙的含量比血压正常的患者高[13]。因此，本研究认为饮食调整在高血压患者中起着重要作用，同时也可以降低结石复发风险。此外，一部分高血压患者服用利尿药物，尤其是噻嗪类药物，可以通过减少尿钙排泄和过饱和来减少结石的复发[14]。研究[15]表明，无可靠的证据表明吸烟与泌尿系结石的发生和复发相关，然而这与本研究结论相反，吸烟增高了结石术后复发率。本研究另一个重要结论是，年轻患者结石复发的可能性更高，而患者的性别并不影响复发率。KANG H W等[16]研究结果显示，术后3年随访过程中，超过40%的年轻患者结石复发，是60岁以上患者的2倍，这可能与年轻人相较老年人更轻视健康状况，从而忽视了结石复发的可能性，术后规律随访的依从性相对较差有关。
综上所述，泌尿系结石患者接受腔内手术治疗后结石复发状况较为常见。糖尿病和吸烟是结石复发的危险性因素，而年龄大和高血压是减少结石复发的保护性因素。
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表 1 不同改良Mayo评分分级的UC患者CRP、ESR水平比较(x±s)
指标 重度(n=7) 中度(n=14) 轻度(n=5) CRP/(mg/L) 12.83±1.54*# 8.64±2.38* 4.72±1.51 ESR/(mm/h) 27.00±5.13*# 16.57±4.50* 10.80±4.55 CRP: C反应蛋白; ESR: 红细胞沉降率。
与轻度患者比较, * P＜0.05; 与中度患者比较, #P＜0.05。
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表 2 不同肠镜评分分级的UC患者CRP、ESR水平比较(x±s)
指标 重度(n=6) 中度(n=11) 轻度(n=9) CRP/(mg/L) 12.92±1.66*# 9.49±2.62* 5.83±1.77 ESR/(mm/h) 27.00±5.62 *# 19.09±4.48* 11.44±3.78 CRP: C反应蛋白; ESR: 红细胞沉降率。
与轻度患者比较, * P＜0.05; 与中度患者比较, #P＜0.05。
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表 3 不同中医证型患者CRP、ESR水平比较(x±s)
指标 大肠湿热证(n=12) 脾肾两虚证(n=14) CRP/(mg/L) 11.17±2.97* 7.17±2.67 ESR/(mm/h) 23.25±6.62* 14.00±4.98 CRP: C反应蛋白; ESR: 红细胞沉降率。
与脾肾两虚证比较, * P＜0.05。
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表 4 不同中医证型在不同改良Mayo评分分级患者中的分布情况[n(%)]
证型 n 重度(n=7) 中度(n=15) 轻度(n=5) 大肠湿热证 12 6(50.00)* 6(50.00) 0 脾肾两虚证 14 1(7.14) 8(57.14) 5(35.71) 与脾肾两虚证比较, * P＜0.05。
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表 5 不同中医证型在不同肠镜评分分级患者中的分布情况[n(%)]
证型 n 重度(n=6) 中度(n=11) 轻度(n=9) 大肠湿热证 12 5(41.67)* 6(50.00) 1(8.33) 脾肾两虚证 14 1(7.14) 5(35.71) 8(57.14) 与脾肾两虚证比较, * P＜0.05。
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