牙周治疗改善非酒精性脂肪性肝病的探索性研究

doi:10.16138/j.1673-6087.2024.03.03

摘要/Abstract

摘要：

目的：研究牙龈卟啉单胞菌（Porphyromonas gingivalis，P.g）对非酒精性脂肪性肝病 (non-alcoholic fatty liver diease， NAFLD) 的影响及牙周治疗对NAFLD的作用。方法：将高脂饮食喂养4周的小鼠随机分为对照组和丝线结扎+涂抹P.g组2组，每组8只，干预4周后处死，检测小鼠肝脏、炎症因子等变化。8例合并牙周病的NAFLD患者随机分为龈下刮治组和刷牙组各4例，牙周治疗组接受龈下刮治术,检测2组患者干预前后的牙周、肝脏等变化。结果：结扎涂抹组较对照组小鼠肝重指数、脂质沉积的形成以及血清脂质、天冬氨酸转氨酶以及铁蛋白水平增加，血清炎症介质表达水平增加（均P<0.05）。与刷牙组受试者相比，龈下刮治组P.g-lgG抗体滴度、探诊深度等牙周指标出现下降，肝脂肪含量等也出现下降趋势，但差异均无统计学意义（P>0.05）。结论：牙周局部感染P.g会加速高脂饮食喂养小鼠NAFLD的进程，牙周治疗对牙周感染关联性NAFLD具有一定的缓解作用。

关键词: 龈下刮治, 牙周病, 非酒精性脂肪性肝病, 牙龈卟啉单胞菌

Abstract:

Objective To study the effect of Porphyromonas gingivalis (P.g) on non-alcoholic fatty liver disease (NAFLD) and the ameliorative effect of periodontal treatment on NAFLD. Methods Mice fed a high-fat diet for 4 weeks were randomly divided into two groups, and there were 8 mice in each group. Group A was blank control, and Group B was given suture ligation + smeared P.g. They were sacrificed after 4 weeks of intervention, and the changes in liver, inflammatory factors were tested. Eight NAFLD patients with periodontal disease were randomly divided into the subgingival scaling group and the control group (4 in each group), and the subgingival scaling group received the basic periodontal treatment. Changes in periodontal status, liver, and blood biochemistry before and after the intervention were tested in the 2 group patients. Results Compared with the control mouse group, the ligation and smear mouse group had increased liver weight, formation of lipid deposits, serum lipid, aspartate transaminase and ferritin levels, and the expression of serum inflammatory mediators was increased. Compared with the patients in the tooth brushing group, the subgingival scraping patient group showed a significantly decreased indexes such as P.g-IgG antibody titer, probing depth, as well as a downward trend in liver fat content, but the differences were not statistically significant （P>0.05）. Conclusions P.g infection can accelerate the progression of NAFLD in mice with high-fat diet, and the periodontal treatment in patients showed a mitigating effect on periodontal infection-associated NAFLD.

Key words: Subgingival scaling, Periodontal disease, Non-alcoholic fatty liver disease, Porphyromonas gingivalis

中图分类号:

R575.5

段中华, 马雪莹, 吴玉琼, 舒家恩, 吴沛, 郭斯敏, 王宇华. 牙周治疗改善非酒精性脂肪性肝病的探索性研究[J]. 内科理论与实践, 2024, 19(03): 167-173.

DUAN Zhonghua, MA Xueying, WU Yuqiong, SHU Jiaen, WU Pei, GUO Simin, WANG Yuhua. An exploratory study of periodontal therapy to improve non-alcoholic fatty liver disease[J]. Journal of Internal Medicine Concepts & Practice, 2024, 19(03): 167-173.

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时间(d)	对照组	结扎+涂抹P.g菌组	t	P
0	22.52±0.47	22.39±0.50	0.561	0.583
4	24.34±0.64	23.82±0.59	1.667	0.118
7	25.18±0.66	25.01±0.67	0.520	0.611
11	26.15±0.88	25.56±0.73	1.462	0.166
14	26.79±1.23	26.27±0.76	1.023	0.324
18	27.36±1.32	27.21±0.84	0.271	0.790
21	28.42±1.43	28.19±1.03	0.363	0.722
24	28.92±1.67	28.86±0.96	0.092	0.928
28	30.13±1.90	29.86±1.19	0.350	0.731
32	30.43±1.00	27.74±1.89	3.138	0.009
36	30.71±1.72	27.45±2.92	2.425	0.032
40	32.05±2.12	27.66±2.72	3.268	0.007
44	32.58±1.95	29.06±2.62	2.756	0.017
48	33.72±1.95	28.83±4.15	2.651	0.021
52	33.98±1.98	35.75±2.05	2.364	0.038
56	35.75±2.05	29.40±4.70	2.804	0.019

项目	对照组	结扎+涂抹P.g菌组	t	P
TG(mmol/L)	1.16±0.07	2.07±0.33	4.479	0.009
总胆固醇(mmol/L)	4.46±1.04	4.48±0.85	0.032	0.975
AST(mmol/L)	210.11±88.62	475.52±159.19	2.962	0.021
ALT(mmol/L)	69.07±36.93	133.42±98.07	1.063	0.329

项目	对照组	结扎+涂抹P.g菌组	t	P
TNF-α	340.17±47.95	504.62±61.19	4.593	<0.001
IL-1β	54.68±3.26	76.33±12.68	3.287	0.007
IL-6	57.54±10.44	82.40±2.88	5.674	<0.001
铁蛋白	13.21±3.79	18.82±3.83	2.727	0.010

项目	刷牙组					龈下刮治组
项目	0个月	3个月	6个月	ΔE_3-0	ΔE_6-0	0个月	3个月	6个月	ΔE_3-0	ΔE_6-0
P.g-lgG抗体滴度（ng/mL）	4.93±0.04	4.70±0.77	4.19±0.41	-0.23±0.81^1）	-0.74±0.4^1）	5.11±0.29^2）	3.57±0.56	3.47±0.93	-1.54±0.32^1）2）	-1.64±0.65^1）2）
PD（mm）	3.15±0.46	2.96±0.50	3.02±0.65	-0.19±0.34^1）	-0.14±0.24^1）	3.66±1.46^2）	3.19±1.20	3.13±1.19	-0.47±0.37^1）2）	-0.53±0.34^1）2）
CAL（mm）	3.61±0.58	3.39±0.31	3.54±0.42	-0.21±0.33^1）	-0.06±0.24^1）	3.82±1.91^2）	3.28±1.12	3.42±1.72	-0.54±1.00^1）2）	-0.39±0.33^1）2）
菌斑指数（分）	2.09±0.17	1.40±0.15	1.51±0.10	-0.69±0.20^1）	-0.58±0.18^1）	1.87±0.37^2）	1.35±0.31	1.43±0.21	-0.52±0.23^1）2）	-0.44±0.36^1）2）
探诊出血百分数（%）	49.75±4.71	43.90±5.23	44.50±4.43	-5.85±3.37^1）	-5.25±2.12^1）	59.28±11.22^2）	44.40±8.97	38.83±11.05	-14.88±18.23^1）2）	-20.45±18.37^1）2）
BMI（kg/m²）	27.65±5.09	27.90±5.06	27.65±5.07	0.25±0.64^1）	0.00±0.43^1）	26.85±1.26^2）	26.35±1.40	26.88±1.49	-0.50±0.93^1）2）	0.03±0.72^1）2）

项目	刷牙组					龈下刮治组
项目	0个月	3个月	6个月	ΔE_3-0	ΔE_6-0	0个月	3个月	6个月	ΔE_3-0	ΔE_6-0
肝脏脂肪含量CAP（db/m）	285.00±39.41	290.25±32.94	287.50±45.99	5.25±27.16^1）	2.50±65.37^1）	273.75±39.82^2）	248.50±24.69	264.50±45.57	-25.25±33.57^1）2）	-9.25±26.59^1）2）
AST（U/L）	30.75±6.24	28.25±8.66	31.00±4.69	-2.50±4.51^1）	0.25±3.20^1）	28.50±5.97^2）	20.25±1.71	23.00±3.46	-8.25±4.57^1）2）	-5.50±9.00^1）2）
ALT（U/L）	36.25±5.12	32.25±7.37	38.50±2.38	-4.00±8.83^1）	2.25±7.27^1）	37.75±11.62^2）	20.25±4.03	26.00±1.15	-17.50±9.47^1）2）	-11.75±12.42^1）2）
肝脏硬度TE（kPa）	5.43±1.15	5.30±0.81	6.78±1.96	-0.13±1.37^1）	1.35±2.26^1）	5.08±0.96^2）	5.63±2.25	5.00±0.36	0.55±2.47^1）2）	-0.08±0.88^1）2）
Ⅳ型胶原（ng/mL）	31.06±12.03	29.72±20.35	29.42±6.80	-1.35±21.63^1）	-1.64±6.40^1）	30.52±11.66^2）	26.21±7.51	23.27±9.53	-4.31±6.71^1）2）	-7.25±7.87^1）2）
总胆固醇（mmol/L）	4.98±0.39	5.47±0.73	5.50±1.17	0.48±0.45^1）	0.52±1.26^1）	5.32±1.15^2）	5.61±0.70	5.31±1.08	0.29±0.47^1）2）	-0.01±0.40^1）2）