髋关节发育不良合并骨关节炎患者血清标志物表达

doi:10.3877/cma.j.issn.1674-134X.2024.01.004

目的

探讨血清肝素结合性表皮生长因子(HB-EGF)、CC类趋化因子配体5(CCL5)在髋关节发育不良(DDH)并发骨关节炎患者中表达情况及临床意义。

方法

本研究纳入邢台市第三医院收治的180例DDH患者设为研究组，排除合并血液系统疾病、代谢性疾病、风湿性免疫疾病、重要脏器功能衰竭、恶性肿瘤、全身炎性疾病以及长期使用免疫抑制剂、糖皮质激素、非甾体类抗炎药的患者，根据有无并发骨关节炎将其分为并发组(72例)和未并发组(108例)。另同期选取180例健康体检者设为对照组。所有受试者均检测血清HB-EGF、CCL5水平。根据Tonnis分级标准判定骨关节炎严重程度，对比骨关节炎不同严重程度DDH患者的血清HB-EGF、CCL5水平，采用多因素logistic回归分析DDH患者并发骨关节炎的影响因素，并采用Spearman相关性分析法分析血清HB-EGF、CCL5表达水平与DDH患者骨关节炎严重程度的关系。

结果

研究组血清HB-EGF、CCL5水平高于对照组(t＝29.933、14.021，均为P<0.001)；并发组年龄、Crowe分型Ⅲ～Ⅳ型患者占比及血清HB-EGF、CCL5水平均高于未并发组(t＝8.857、χ²＝7.018、t＝12.025、t＝8.536，均为P<0.05)；年龄[比值比(OR)＝1.504，95%置信区间(CI)(1.132，2.457)，P＝0.014]、Crowe分型[OR＝2.347，95%CI(1.568，3.742)，P<0.001]、血清HB-EGF水平[OR＝1.994，95%CI(1.472，2.993)，P<0.001]、血清CCL5水平[OR＝1.548，95%CI(1.055，2.602)，P＝0.007]均是DDH患者并发骨关节炎的独立影响因素；骨关节炎不同严重程度DDH患者血清HB-EGF、CCL5水平差异有统计学意义(F＝27.255、12.855，均为P<0.05)，2级和3级均高于1级(2级t＝5.599、5.749，3级t＝3.669、3.803，均为P<0.05)，3级高于2级(t＝2.157、2.232，均为P<0.05)；血清HB-EGF、CCL5表达水平与DDH患者骨关节炎严重程度呈正相关(r＝0.628、0.497，均为P<0.05)。

结论

血清HB-EGF、CCL5在DDH患者中表达上调，在DDH并发骨关节炎中表达水平更高，与骨关节炎严重程度呈正相关，且是DDH患者并发骨关节炎的独立影响因素。

关键词: 发育性髋关节发育不良, 骨关节炎, 肝素结合EGF样生长因子, 趋化因子CCL5, 数据相关性

Objective

To investigate the expression and clinical significance of serum heparin binding epidermal growth factor (HB-EGF) and CC chemokine ligand 5 (CCL5) in patients with hip dysplasia (DDH) complicated with osteoarthritis.

Methods

This study included 180 DDH patients admitted to Xingtai Third Hospital as the study group, excluding patients with concomitant hematological diseases, metabolic diseases, rheumatic immune diseases, important organ failure, malignant tumors, systemic inflammatory diseases, as well as long-term use of immunosuppressants, glucocorticoids, and nonsteroidal anti-inflammatory drugs. They were divided into the complicated group (72 cases) and the non complicated group (108 cases) according to the presence or absence of osteoarthritis. In addition, 180 healthy people were selected as the control group at the same time. Serum HB-EGF and CCL5 levels of all subjects were detected. The severity of osteoarthritis was determined according to the Tonnis grading standard, and the levels of serum HB-EGF and CCL5 in DDH patients with different severity of osteoarthritis were compared. The influencing factors of osteoarthritis in patients with DDH were analyzed by multivariate logistic regression, and the relationship between the expression levels of serum HB-EGF and CCL5 and the severity of osteoarthritis in patients with DDH was analyzed by Spearman correlation analysis.

Results

The levels of serum HB-EGF and CCL5 in the study group were higher than those in the control group(t =29.933, 14.021, both P<0.001). Age, proportion of patients with Crowe type Ⅲ-Ⅳ and serum HB-EGF and CCL5 levels in the complicated group were higher than those in the uncomplicated group (t =8.857, χ²=7.018, t =12.025, t =8.536, all P<0.05). Age[odds ratio (OR)=1.504, 95% confidence interval (CI) (1.132, 2.457), P=0.014], Crowe's classification[OR =2.347, 95%CI (1.568, 3.742), P<0.001], serum HB-EGF [OR =1.994, 95%CI (1.472, 2.993), P<0.001] and serum CCL5 [OR =1.548, 95%CI (1.055, 2.602), P =0.007]were the independent influencing factors of osteoarthritis in DDH patients. The levels of serum HB-EGF and CCL5 in DDH patients with different severity of osteoarthritis were significantly different (F =27.255, 12.855, both P<0. 05), and level two and three were higher than level one (level two t =5.599, 5.749, level three t=3.669, 3.803, all P <0.05), and level three was higher than level two (t =2.157, 2.232, both P<0.05). The expression levels of serum HB-EGF and CCL5 were positively correlated with the severity of osteoarthritis in DDH patients (r =0.628, 0.497, both P<0.05).

Conclusion

Serum HB-EGF and CCL5 are up-regulated in patients with DDH, and the expression level is higher in patients with DDH complicated with osteoarthritis, which is positively correlated with the severity of osteoarthritis, and they are independent influencing factor for patients with DDH complicated with osteoarthritis.

Key words: Developmental dysplasia of the hip, Osteoarthritis, Heparin-binding EGF-like growth factor, Chemokine CCL5, Correlation of data

表1 研究组与对照组临床资料

Table 1 Clinical data of the study group and the control group

组别Groups	例数Number of cases	性别[例(%)]Gender		年龄[岁，(±s)]Age	BMI[kg/m²，(±s)]	HB-EGF[mg/L，(±s)]	CCL5[ng/L，(±s)]
组别Groups	例数Number of cases	男Male	女Female	年龄[岁，(±s)]Age	BMI[kg/m²，(±s)]	HB-EGF[mg/L，(±s)]	CCL5[ng/L，(±s)]
研究组Study group	180	64(35.6)	116(64.4)	39.3±6.6	23.1±2.1	15.3±5.0	429.2±63.1
对照组Control group	180	69(38.3)	111(61.7)	38.7±8.1	23.2±2.2	3.9±1.2	339.5±58.3
统计值Statistical value		χ²＝0.298		t＝0.797	t＝0.390	t＝29.933	t＝14.021
P值		>0.05		>0.05	>0.05	<0.001	<0.001

表1 研究组与对照组临床资料

Table 1 Clinical data of the study group and the control group

组别Groups	例数Number of cases	性别[例(%)]Gender		年龄[岁，(±s)]Age	BMI[kg/m²，(±s)]	HB-EGF[mg/L，(±s)]	CCL5[ng/L，(±s)]
组别Groups	例数Number of cases	男Male	女Female	年龄[岁，(±s)]Age	BMI[kg/m²，(±s)]	HB-EGF[mg/L，(±s)]	CCL5[ng/L，(±s)]
研究组Study group	180	64(35.6)	116(64.4)	39.3±6.6	23.1±2.1	15.3±5.0	429.2±63.1
对照组Control group	180	69(38.3)	111(61.7)	38.7±8.1	23.2±2.2	3.9±1.2	339.5±58.3
统计值Statistical value		χ²＝0.298		t＝0.797	t＝0.390	t＝29.933	t＝14.021
P值		>0.05		>0.05	>0.05	<0.001	<0.001

表2 并发组和未并发组临床资料比较

Table 2 Comparison of clinical data between concurrent and non concurrent groups

临床资料Clinical data	并发组Complication group	未并发组Non complication group	统计值Statistical value	P值
例数Number of cases	72	108
性别[例(%)]Gender
男Male	22(30.6)	42(38.9)
女Female	50(69.4)	66(61.1)	χ²＝1.309	>0.05
年龄[岁，(±s)]Age (years)	44.8±5.1	36.3±6.9	t＝8.857	<0.001
BMI[kg/m²，(±s)]	23.2±2.3	22.9±2.2	t＝0.863	>0.05
病变位置[例(%)]Location of lesion
单侧病变Unilateral lesion	52(72.2)	73(67.6)
双侧病变Bilateral lesions	20(27.8)	35(32.4)	χ²＝0.436	>0.05
Crowe分型[例(%)]Crowe classification
Ⅰ～Ⅱ	33(45.8)	71(65.7)
Ⅲ～Ⅳ	39(54.2)	37(34.3)	χ²＝7.018	0.008
HB-EGF [mg/L，(±s)]	20.8±6.0	11.7±4.1	t＝12.025	<0.001
CCL5 [ng/L，(±s)]	476.3±61.0	397.8±60.0	t＝8.536	<0.001

表2 并发组和未并发组临床资料比较

Table 2 Comparison of clinical data between concurrent and non concurrent groups

临床资料Clinical data	并发组Complication group	未并发组Non complication group	统计值Statistical value	P值
例数Number of cases	72	108
性别[例(%)]Gender
男Male	22(30.6)	42(38.9)
女Female	50(69.4)	66(61.1)	χ²＝1.309	>0.05
年龄[岁，(±s)]Age (years)	44.8±5.1	36.3±6.9	t＝8.857	<0.001
BMI[kg/m²，(±s)]	23.2±2.3	22.9±2.2	t＝0.863	>0.05
病变位置[例(%)]Location of lesion
单侧病变Unilateral lesion	52(72.2)	73(67.6)
双侧病变Bilateral lesions	20(27.8)	35(32.4)	χ²＝0.436	>0.05
Crowe分型[例(%)]Crowe classification
Ⅰ～Ⅱ	33(45.8)	71(65.7)
Ⅲ～Ⅳ	39(54.2)	37(34.3)	χ²＝7.018	0.008
HB-EGF [mg/L，(±s)]	20.8±6.0	11.7±4.1	t＝12.025	<0.001
CCL5 [ng/L，(±s)]	476.3±61.0	397.8±60.0	t＝8.536	<0.001

表3 DDH患者并发骨关节炎的多因素logistic回归分析

Table 3 Multivariate logistic regression analysis of osteoarthritis in DDH patients

变量Variables	β值	SE	Wald χ²值	P值	OR值	95% CI
年龄Age	0.408	0.166	6.041	0.014	1.504	(1.132，2.457)
Crowe Ⅰ～Ⅱ	－	－	－	－	参考	－
Crowe Ⅲ～Ⅳ	0.853	0.272	9.835	<0.001	2.347	(1.568，3.742)
HB-EGF	0.690	0.214	10.396	<0.001	1.994	(1.472，2.993)
CCL5	0.437	0.159	7.554	0.007	1.548	(1.055，2.602)

表3 DDH患者并发骨关节炎的多因素logistic回归分析

Table 3 Multivariate logistic regression analysis of osteoarthritis in DDH patients

变量Variables	β值	SE	Wald χ²值	P值	OR值	95% CI
年龄Age	0.408	0.166	6.041	0.014	1.504	(1.132，2.457)
Crowe Ⅰ～Ⅱ	－	－	－	－	参考	－
Crowe Ⅲ～Ⅳ	0.853	0.272	9.835	<0.001	2.347	(1.568，3.742)
HB-EGF	0.690	0.214	10.396	<0.001	1.994	(1.472，2.993)
CCL5	0.437	0.159	7.554	0.007	1.548	(1.055，2.602)

表4 骨关节炎不同严重程度DDH患者血清HB-EGF、CCL5水平(

±s)

Table 4 Serum HB-EGF and CCL5 levels in DDH patients with different severity of osteoarthritis

病情分级Disease grading	例数Number of cases	HB-EGF(mg/L)	CCL5(ng/L)
1级Level 1	49	18.2±4.4	450.6±71.1
2级Level 2	18	25.2±4.9^a	518.9±56.3^a
3级Level 3	5	29.8±2.8^ab	574.0±37.8^ab
F值		27.255	12.855
P值		<0.001	<0.001

表4 骨关节炎不同严重程度DDH患者血清HB-EGF、CCL5水平(

±s)

Table 4 Serum HB-EGF and CCL5 levels in DDH patients with different severity of osteoarthritis

病情分级Disease grading	例数Number of cases	HB-EGF(mg/L)	CCL5(ng/L)
1级Level 1	49	18.2±4.4	450.6±71.1
2级Level 2	18	25.2±4.9^a	518.9±56.3^a
3级Level 3	5	29.8±2.8^ab	574.0±37.8^ab
F值		27.255	12.855
P值		<0.001	<0.001

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Expression of serum biomarkers in patients with hip dysplasia complicated with osteoarthritis

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Expression of serum biomarkers in patients with hip dysplasia complicated with osteoarthritis