自拟中药组方化石汤预防上尿路结石术后复发的研究

Study on Prevention of Postoperative Recurrence of Upper Urinary Tract Stones by Self-Proposed Traditional Chinese Medicine Formula Hua Shi Tang

摘要: 目的：探究中药组方化石汤对上尿路结石术后复发的预防作用。方法：随访潍坊市人民医院60例经治疗后结石全部排出的临床痊愈的上尿路结石患者，采用随机单盲对照的方法，验证自拟中药组方化石汤对上尿路结石患者预防的疗效；并应用大鼠草酸钙结石模型加以验证，探究其可能的作用机制。结果：临床研究中两组患者的基本情况的比较：年龄(44.23 ± 2.37岁vs 45.47 ± 2.94岁)、性别(70%:30% vs 63.3%:36.7%)的差异无统计学意义(P > 0.05)。结石复发率(3.3% vs 16.7%)的差异无统计学意义(P > 0.05)，尿液生化检测方面，尿PH值(6.4 ± 0.55 vs 5.9 ± 1.14)、尿UA (2.85 ± 0.76 mmol/L vs 3.31 ± 0.95 mmol/L)、尿Ox (0.43 ± 0.32 mmol/L vs 0.61 ± 0.38 mmol/L)的差异存在统计学意义(P < 0.05)。尿Ca (4.53 ± 1.06 mmol/L vs 5.24 ± 0.95 mmol/L)的差异则具有显著统计学意义(P < 0.01)。动物研究方面：大鼠尿液检测指标中，尿Ca：空白组与结石组(0.29 ± 0.06 mmol/L vs 0.39 ± 0.06 mmol/L)相比，差异存在显著统计学意义(P < 0.01)，化石汤组与结石组(0.33 ± 0.08 mmol/L vs 0.39 ± 0.06 mmol/L)相比，差异有统计学意义(P < 0.05)，但空白组与化石汤组(0.29 ± 0.06 mmol/L vs 0.33 ± 0.08 mmol/L)相比较，差异无统计学意义(P > 0.05)。尿Mg：空白组与结石组(0.86 ± 0.07 mmol/L vs 0.63 ± 0.06 mmol/L)比较，差异存在显著统计学意义(P < 0.01)，化石汤组与结石组(0.75 ± 0.12 mmol/L vs 0.63 ± 0.06 mmol/L)相比，差异有统计学意义(P < 0.05)，化石汤组与空白组(0.75 ± 0.12 mmol/L vs 0.86 ± 0.07 mmol/L)相比较，差异具有统计学意义(P < 0.05)。尿Ox：空白组与结石组(0.24 ± 0.03 mmol/24 h vs 0.39 ± 0.03 mmol/24 h)的差异存在显著统计学意义(P < 0.01)，化石汤组与结石组(0.31 ± 0.08 mmol/24 h vs 0.39 ± 0.03 mmol/24 h)相比较，差异具有显著统计学意义(P < 0.01)，空白组与化石汤组(0.24 ± 0.03 mmol/24 h vs 0.31 ± 0.08 mmol/24 h)相比差异有统计学意义(P < 0.05)。大鼠血液指标中，BUN：空白组、化石汤组与结石组 (9.03 ± 0.75 mmol/L、10.12 ± 1.17 mmol/L vs 13.25 ± 0.89 mmol/L)相比，差异存在显著统计学意义(P < 0.01)，空白组与化石汤组相比(9.03 ± 0.75 mmol/L vs 10.12 ± 1.17 mmol/L)差异具有统计学意义(P < 0.05)。血清Cr：空白组与化石汤组和结石组(26.13 ± 1.86 μmol/L、29.84 ± 2.43 μmol/L vs 34.46 ± 5.23 μmol/L)相比，差异存在显著统计学意义(P < 0.01)，空白组与化石汤组(26.13 ± 1.86 μmol/L vs 29.84 ± 2.43 μmol/L)相比较，差异具有统计学意义(P < 0.05)。空白组、结石组以及化石汤组的血清Ca (2.13 ± 0.27 mmol/L vs 2.21 ± 0.45 mmol/L vs 2.14 ± 0.38 mmol/L)、血清P (2.78 ± 0.41 mmol/L vs 2.96 ± 0.32 mmol/L vs 2.83 ± 0.14 mmol/L)浓度结果差异均无统计学意义(P > 0.05)。大鼠肾指数：结石组较空白组、化石汤组肾脏明显增大(1.04% ± 0.22% vs 0.93% ± 0.12%、0.97% ± 0.21%)，但差异均无统计学意义(P > 0.05)。大鼠肾组织Elisa检测指标结果：超氧化物歧化酶(SOD)活力结果：空白组、化石汤组与结石组(128.43 ± 23.76 U/mgprot、98.63 ± 19.36 U/mgprot vs 56.13 ± 12.14 U/mgprot)相比，差异具有显著统计学意义(P < 0.01)，空白组与化石汤组(128.43 ± 23.76 U/mgprot vs 98.63 ± 19.36 U/mgprot)相比，差异具有统计学意义(P < 0.01)。丙二醛(MDA)含量：空白组、化石汤组与结石组(2.73 ± 0.36 U/mgprot、3.13 ± 0.43 U/mgprot vs 4.32 ± 0.21 U/mgprot)相比，差异具有显著统计学意义(P < 0.01)，空白组与化石汤组(2.73 ± 0.36 U/mgprot vs 3.13 ± 0.43 U/mgprot)相比，差异具有统计学意义(P < 0.05)。大鼠肾组织病理：空白组无明显异常，肾小管无明显扩张且无草酸钙结晶出现，结石组镜下可见肾小管内连接成片的草酸钙结晶，且肾小管扩张明显，化石汤组镜下可见肾小管内有散在的草酸钙结晶，肾小管扩张明显轻于结石组，接近于空白组。

Abstract: Objective: To investigate the preventive effect of the Chinese herbal formula Hua Shi Tang on postoperative recurrence of upper urinary tract stones. Methods: Weifang People’s Hospital followed up 60 clinically cured patients with upper urinary tract stones who had all stones discharged after treatment, and used a randomized single-blind controlled method to verify the efficacy of the self-proposed traditional Chinese medicine formula Hua Shi Tang on the prevention of patients with upper urinary tract stones; and applied the rat calcium oxalate stone model to verify it, and to explore the possible mechanism of its action. Results: There were no significant differences in age (44.23 ± 2.37 years vs 45.47 ± 2.94 years) and gender (70%:30% vs 63.3%:36.7%) between the two groups in the clinical study (P > 0.05). There was no significant difference in stone recurrence rate (3.3% vs 16.7%) (P > 0.05). Among urinary PH (6.4 ± 0.55 vs 5.9 ± 1.14), urinary UA (2.85 ± 0.76 mmol/L vs 3.31 ± 0.95 mmol/L), urinary Ox (0.43 ± 0.32 mmol/L vs 0.61 ± 0.38 mmol/L), the differences were statistically significant (P < 0.05). Urinary Ca (4.53 ± 1.06 mmol/L vs 5.24 ± 0.95 mmol/L) was significantly different (P < 0.01). Animal Studies: In rat urine detection indicators, urine Ca: There was a statistically significant difference between the blank group and the stone group (0.29 ± 0.06 mmol/L vs 0.39 ± 0.06 mmol/L) (P < 0.01). Compared with the stone group and the Hua Shi Tang group (0.33 ± 0.08 mmol/L vs 0.39 ± 0.06 mmol/L), the difference was statistically significant (P < 0.05), but there was no statistically significant difference between the blank group and Hua Shi Tang group (0.29 ± 0.06 mmol/L vs 0.33 ± 0.08 mmol/L) (P > 0.05). Urinary Mg: There was a statistically significant difference between the blank group and the stone group (0.86 ± 0.07 mmol/L vs 0.63 ± 0.06 mmol/L) (P < 0.01). Compared with the stone group and the Hua Shi Tang group (0.75 ± 0.12 mmol/L vs 0.63 ± 0.06 mmol/L), the difference was statistically significant (P < 0.05). Compared with the blank group (0.75 ± 0.12 mmol/L vs 0.86 ± 0.07 mmol/L), the difference was statistically significant (P < 0.05). Urine Ox: The difference between the blank group and the stone group (0.24 ± 0.03 mmol/24 h vs 0.39 ± 0.03 mmol/24 h) was statistically significant (P < 0.01). There was a significant difference between the Hua Shi Tang group and stone group (0.31 ± 0.08 mmol/24 h vs 0.39 ± 0.03 mmol/24 h) (P < 0.01). There was a significant difference between the blank group and the Hua Shi Tang group (0.24 ± 0.03 mmol/24 h vs 0.31 ± 0.08 mmol/24 h) (P < 0.05). In the blood indexes of rats, BUN: There was a significant difference between the blank group, Hua Shi Tang group, and stone group (9.03 ± 0.75 mmol/L, 10.12 ± 1.17 mmol/L vs 13.25 ± 0.89 mmol/L) (P < 0.01). The difference between the blank group and the Hua Shi Tang group (9.03 ± 0.75 mmol/L vs 10.12 ± 1.17 mmol/L) was statistically significant (P < 0.05). Serum Cr: There was a significant difference between the blank group, Hua Shi Tang group, and stone group (26.13 ± 1.86 μmol/L, 29.84 ± 2.43 μmol/L vs 34.46 ± 5.23 μmol/L) (P < 0.01). The difference between the blank group and the Hua Shi Tang group (26.13 ± 1.86 μmol/L vs 29.84 ± 2.43 μmol/L) was statistically significant (P < 0.05). The serum calcium concentrations in the blank group, stone group, and Hua Shi Tang group were 2.13 ± 0.27 mmol/L, 2.21 ± 0.45 mmol/L, and 2.14 ± 0.38 mmol/L, respectively. The serum phosphorus concentrations were 2.78 ± 0.41 mmol/L, 2.96 ± 0.32 mmol/L, and 2.83 ± 0.14 mmol/L, respectively. There were no significant differences in serum calcium and serum phosphorus concentrations among the groups (P > 0.05). Kidney index of rats: The kidney of the stone group was significantly increased compared with the blank group and fossil decoction group (1.04% ± 0.22% vs 0.93% ± 0.12%, 0.97% ± 0.21%), but there was no statistical significance (P > 0.05). Elisa test results of rat kidney tissue: Superoxide dismutase (SOD) activity results: There was a significant difference between the blank group, Hua Shi Tang group, and lithiasis group (128.43 ± 23.76 U/mgprot, 98.63 ± 19.36 U/mgprot vs 56.13 ± 12.14 U/mgprot) (P < 0.01). The difference between the blank group and the Hua Shi Tang group (128.43 ± 23.76 U/mgprot vs 98.63 ± 19.36 U/mgprot) was statistically significant (P < 0.01). Malondialdehyde (MDA) content: The difference between the blank group and Hua Shi Tang group and stone group (2.73 ± 0.36 U/mgprot, 3.13 ± 0.43 U/mgprot vs 4.32 ± 0.21 U/mgprot) was statistically significant (P < 0.01). The difference between the blank group and the Hua Shi Tang group (2.73 ± 0.36 U/mgprot vs 3.13 ± 0.43 U/mgprot) was statistically significant (P < 0.05). Renal histopathology of rats: in the blank group, there were no obvious abnormalities, no obvious expansion of renal tubules and no calcium oxalate crystals; in the calculus group, calcium oxalate crystals connected into renal tubules were visible under the microscope, and renal tubule dilation was obvious; in the Hua Shi Tang group, scattered calcium oxalate crystals were visible in renal tubules under the microscope, and renal tubule dilation was significantly less than that in the calculus group and close to that in the blank group.