發(fā)布時間：2018-07-06 16:05

  本文選題：化瘀健脾防石湯 + 結(jié)石抑制物��； 參考：《中國中醫(yī)科學院》2016年博士論文

【摘要】：泌尿系結(jié)石是最常見的泌尿科疾病之一。近年來,隨著氣候變暖及高血脂、高血糖、高血壓等代謝性疾病患者的增加,泌尿系路結(jié)石發(fā)病率呈明顯增長趨勢。泌尿系結(jié)石是一個高復(fù)發(fā)疾病,10年復(fù)發(fā)率達到50%。如此高的復(fù)發(fā)率不但增加了患者的痛苦及經(jīng)濟負擔,多次的ESWL及手術(shù)治療可導致輸尿管狹窄、腎萎縮、及腎臟功能損害等并發(fā)癥。因此,針對其病因的診斷和預(yù)防性治療越來越受到重視。由于泌尿系結(jié)石的病因非常復(fù)雜,是多種因素共同作用的結(jié)果。所以結(jié)石的預(yù)防是一個系統(tǒng)工程,很多人非常注意基礎(chǔ)預(yù)防,但結(jié)石仍然復(fù)發(fā),長期服用枸櫞酸鹽類藥物會造成胃腸道刺激等副作用,無法長期堅持。中草藥對泌尿系結(jié)石的預(yù)防確有療效,且副作用小,并可以整體調(diào)理,改善患者的易成石體質(zhì),但仍然需要系統(tǒng)的臨床及基礎(chǔ)研究進行驗證�；谥嗅t(yī)“治未病”的思想,繼承發(fā)展名老中醫(yī)防治泌尿系結(jié)石的經(jīng)驗,我們將劉猷枋教授、張亞強教授破血行氣、化瘀軟堅的治療尿石癥的思想與高榮林教授調(diào)理脾胃、化濕消滯的防治泌尿系結(jié)石經(jīng)驗加以總結(jié)綜合。在化瘀尿石湯的基礎(chǔ)上化裁出化瘀健脾防石湯。在臨床應(yīng)用中表現(xiàn)出良好的預(yù)防泌尿系結(jié)石的療效。傳統(tǒng)觀點認為尿液結(jié)晶鹽過飽和是結(jié)石形成的首要因素。然而,目前大量研究表明,人體內(nèi)的一些成分在抑制尿液中晶體的成核,聚集和生長方面起到了至關(guān)重要的作用,稱為結(jié)石抑制物。在正常人的尿液中結(jié)石抑制物具有較高的濃度及活性,所以結(jié)石不容易形成。但當尿中結(jié)石抑制物濃度下降或結(jié)構(gòu)改變時,對成石的抑制能力就會下降,就容易導致結(jié)石的生成。尿中枸櫞酸鹽、尿鎂離子的濃度及THP, OPN和ITIH3的表達在結(jié)石的發(fā)生、發(fā)展過程中起重要作用。而化瘀健脾防石湯也是以活血化瘀,健脾利濕為立法,通過整體調(diào)理改善患者的易成石體質(zhì)�；诖�,我們推測化瘀健脾防石湯對尿路結(jié)石的防治機理可能與調(diào)控結(jié)石抑制物的濃度及表達有關(guān)。因此,在高榮林老師、張亞強老師的指導下設(shè)計了以下臨床試驗進行驗證。研究目的：驗證化瘀健脾防石湯對泌尿系結(jié)石患者尿中主要小分子結(jié)石抑制物枸櫞酸鹽、鎂,大分子結(jié)石抑制物THP蛋白、骨橋蛋白(0PN)、間α-胰蛋白酶抑制物重鏈H3(ITIH3)的影響。探索化瘀健脾防石湯預(yù)防泌尿系結(jié)石的作用機制。為臨床用藥及進一步研究提供依據(jù)。研究方法：總體設(shè)計采用隨機單盲安慰劑對照的方法,選擇廣安門醫(yī)院2015年1月至2015年8月期間,60例經(jīng)治療后結(jié)石全部排出的臨床痊愈患者,隨機分成化瘀健脾防石湯治療組和安慰劑對照組,每組30人。經(jīng)過4周的治療,進入最后的療效分析。1.納入病例標準：(1)年齡18-60歲(2)曾診斷為泌尿系結(jié)石(上尿路)(3)符合泌尿系結(jié)石(上尿路)治愈標準(4)符合氣滯血瘀脾虛濕阻證的辯證標準(5)簽署知情同意書2.排除病例標準：(1)合并腎或輸尿管畸形、輸尿管狹窄的患者(2)合并泌尿系統(tǒng)腫瘤的患者(3)合并腎盂腎炎及輸尿管炎等上尿路感染的患者(4)合并有嚴重心腦血管疾病,肝腎及造血系統(tǒng)嚴重原發(fā)病的患者(5)甲狀旁腺功能亢進的患者(6)過敏體質(zhì)者3.治療方法：(1)治療組：化瘀健脾防石湯一次1袋一日2次。連續(xù)服用4周(2)對照組：化瘀健脾防石湯安慰劑一次1袋一日2次。連續(xù)服用4周4.療程：4周5.觀測指標(1)主要療效指標(入組、服藥4周后各檢測、記錄一次)：①24小時尿尿枸櫞酸、尿鎂②ELISA檢尿液中THP、OPN、ITIH3的蛋白表達③中醫(yī)證侯評分(2)次要療效指標(入組、服藥4周后各檢測一次)①尿PH值②24小時尿尿鈣、尿磷、尿草酸、尿尿酸③血鈣、血磷、血鎂、血尿酸研究結(jié)果：1.可比性分析：入選時兩組間年齡、病程、男女比例、尿TH蛋白、骨橋蛋白、間a-胰蛋白酶抑制物重鏈H3、尿PH值、24小時尿鈣、尿磷、尿草酸、尿尿酸、尿鎂、尿枸櫞酸、血鈣、血磷、血鎂、血尿酸及中醫(yī)證候評分比較,差異均無統(tǒng)計學意義(P均0.05),具有可比性。2.療效分析結(jié)論：2.1主要療效指標2.1.1對主要結(jié)石抑制物療效24小時尿枸櫞酸的排泄總量治療組組內(nèi)治療前后比較差別有統(tǒng)計學意義(P0.01),治療組與對照組療后比較差別有統(tǒng)計學意義(P0.01)。24小時尿枸櫞酸的排泄總量較療前明顯增加。24小時尿鎂的總量治療組與對照組治療前后組內(nèi)比較差別無統(tǒng)計學意義(P0.05),治療后兩組組間比較差別無統(tǒng)計學意義(P0.05)。說明本方對24小時尿鎂的排泄量無影響。尿TH蛋白的濃度在治療組組內(nèi)治療前后的比較中,表現(xiàn)出統(tǒng)計學差異(P0.01)。治療組與對照組療后比較的差異也有統(tǒng)計學意義(P0.05)。TH蛋白的濃度較治療前有所下降。尿OPN蛋白濃度在治療組治療前后的組內(nèi)比較中,差別無統(tǒng)計學意義(P0.05)。療后治療組與對照組比較差別無統(tǒng)計學意義(P0.05)。尿間α-胰蛋白酶抑制物重鏈H3濃度在治療組組內(nèi)治療前后的比較中,表現(xiàn)出統(tǒng)計學差異(P0.01)。治療組與對照組療后比較的差異也有統(tǒng)計學意義(P0.05)。間α-胰蛋白酶抑制物重鏈H3濃度較治療前下降說明化瘀尿石湯確實有預(yù)防結(jié)石復(fù)發(fā)的作用�；鼋∑⒎朗瘻梢栽黾有》肿咏Y(jié)石抑制物尿枸櫞酸的排泄量,可以下調(diào)泌尿系結(jié)石治愈患者尿TH蛋白和尿間α-胰蛋白酶抑制物重鏈H3的異常表達。2.1.2中醫(yī)證候評分療效化瘀健脾防石湯能夠明顯降低治療組患者的中醫(yī)證候評分,總有效率達到79.3%,與安慰劑對照組28.6%的有效率比較,差別有顯著統(tǒng)計學意義(P0.01)。說明化瘀健脾防石湯可改善氣滯血瘀脾虛濕阻證患者的主要臨床癥狀,降低中醫(yī)證候評分,糾正患者血瘀、脾虛、濕阻的易成石體質(zhì)。從根本上預(yù)防泌尿系結(jié)石的復(fù)發(fā)。2.2次要療效指標療后治療組尿PH值呈上高趨勢,與治療前組內(nèi)比較,差異有統(tǒng)計學意義意義(P0.01)；治療組與對照組療后比較差異有統(tǒng)計學意義(P0.01)。療后治療組尿鈣呈下降趨勢。治療組尿鈣組內(nèi)治療前后比較,差異有統(tǒng)計學意義(P0.01)；療后治療組與對照組比較,差異有統(tǒng)計學意義(P0.01)。對24小時尿草酸、尿尿酸、尿磷、血鈣、血磷、血鎂、血尿酸的療效,治療組治療前后的組內(nèi)比較中,差別無統(tǒng)計學意義(P0.05)。療后治療組與對照組比較差別無統(tǒng)計學意義(P0.05)。說明本藥物對以上指標物無影響。研究結(jié)論：從整個臨床試驗看,化瘀健脾防石湯可以增加小分子結(jié)石抑制物尿枸櫞酸的排泄量,可以下調(diào)泌尿系結(jié)石治愈患者尿TH蛋白和尿間α-胰蛋白酶抑制物重鏈H3的異常表達。并有提高患者尿PH值,降低24小時尿鈣總排泄量的作用。同時,化瘀健脾防石湯能夠改善氣滯血瘀、脾虛濕阻證患者的主要臨床癥狀,降低中醫(yī)證候評分,糾正患者血瘀、脾虛、濕阻的易成石體質(zhì)。說明化瘀健脾防石湯可以調(diào)節(jié)泌尿系結(jié)石患者尿中主要結(jié)石抑制物的濃度及表達。并有一定的代謝調(diào)節(jié)作用。這些作用都對泌尿系結(jié)石復(fù)發(fā)的預(yù)防有重要的積極意義。說明化瘀健脾防石湯有進一步觀察研究的價值。下一步針對化瘀健脾防石湯的研究應(yīng)該從兩方面入手,首先,本方雖然組方時間僅有3年,但在臨床應(yīng)用中也表現(xiàn)出了很好的預(yù)防結(jié)石復(fù)發(fā)的療效。但觀察的病例數(shù)和觀察的時間都有欠缺。所以其療效需要一個大樣本、多中心、隨機對照、觀察時間在3年以上的臨床試驗的支持。其次,本試驗只是初步觀察了化瘀健脾防石湯對人尿中主要結(jié)石抑制物的影響。無法了解其對腎組織內(nèi)結(jié)石抑制物表達的影響及其調(diào)控結(jié)石抑制物的主要機理。也不了解其是否對腎小管上皮細胞的損傷有修復(fù)作用。因此需要一個設(shè)計完善的模型動物試驗及體外晶體模型抑制試驗的支持。只有這樣才能全面評價化瘀健脾防石湯對泌尿系結(jié)石復(fù)發(fā)的預(yù)防作用。
[Abstract]:Urolithiasis is one of the most common urological diseases. In recent years, with the increasing of the climate warming and the increase of metabolic diseases such as hyperlipidemia, hyperglycemia and hypertension, the incidence of urinary calculi is obviously increasing. Urolithiasis is a highly recurrent disease. The recurrence rate of such high recurrence rate of 10 years has increased not only in the 10 year recurrence rate. The pain and economic burden of the people, multiple ESWL and surgical treatment can lead to complications such as ureteral stenosis, renal atrophy, and renal dysfunction. Therefore, the diagnosis and preventive treatment of the causes are becoming more and more important. Because the cause of urinary calculi is very complicated, it is the result of multiple factors. So the prevention of calculus It is a systematic project. Many people pay great attention to basic prevention, but the stones still relapse. Long term use of citrate salts can cause gastrointestinal irritation and other side effects, which can not be persisted for a long time. Chinese herbal medicine has a good effect on the prevention of urinary calculi, with small side effects and can improve the Yi Chengshi constitution of the patient as a whole, but still need to improve the patient's constitution. To verify the clinical and basic research of the system, based on the idea of "treating the disease without disease" and inheriting the experience of developing the old traditional Chinese medicine to prevent and cure urolithiasis, we will teach professor Liu Youfang, Professor Zhang Yaqiang to break blood gas, the thought of treating urolithiasis in the treatment of blood stasis and soft backbone, and the treatment of the spleen and stomach by Gao Rong Lin, and the prevention and treatment of urinary calculi. Experience is summarized and comprehensive. On the basis of Huayu urolithiasis soup, Huayu Jianpi prevention stone soup is cut out. In clinical application, it shows a good effect on the prevention of urinary calculi. The traditional view holds that the supersaturation of urine crystal salt is the primary factor for the formation of stones. However, a large number of studies have shown that some of the ingredients in the human body are inhibiting the urine. The nucleation, aggregation and growth of medium crystals play a vital role, known as stone inhibitors. Stone inhibitors have high concentration and activity in normal human urine, so stones are not easy to form. But when the concentration of stone inhibitors decreases or structural changes in urine, the ability to inhibit the formation of stones will be reduced and easy to guide. The formation of lithiasis. The concentration of urinary citrate, urine magnesium ion and the expression of THP, OPN and ITIH3 play an important role in the occurrence and development of the stone, and the Huayu Jianpi anti stone soup is also the legislation of promoting blood circulation to remove blood stasis and invigorating the spleen and dampness, and improving the patient's easy stone constitution through the whole conditioning. Based on this, we speculate that the Huayu Jianpi anti stone soup is used. The mechanism of prevention and control of urinary calculi may be related to the control of the concentration and expression of stone inhibitors. Therefore, the following clinical trials were designed under the guidance of teacher Gao Ronglin and Mr. Zhang Yaqiang. The effect of macromolecular stone inhibitor THP protein, osteopontin (0PN) and inter alpha trypsin inhibitor heavy chain H3 (ITIH3). To explore the mechanism of the effect of Huayu Jianpi anti stone Decoction on the prevention of urinary calculi, and to provide the basis for clinical use and further study. The overall design is a randomized, single blind, placebo-controlled method for choosing Guanganmen. During the period from January 2015 to August 2015, 60 patients with all the clinical healed stones after treatment were randomly divided into the treatment group of Huayu Jianpi anti stone soup and the placebo control group, with 30 people in each group. After 4 weeks of treatment, the final curative effect analysis.1. was included in the case standard: (1) the age 18-60 years (2) had been diagnosed as urinary calculi (upper urinary tract). ) (3) conforming to the standard of urolithiasis (upper urinary tract) cure (4) the dialectical standard of syndrome of stagnation of blood stasis and spleen deficiency syndrome (5) signing informed consent 2. exclusion criteria: (1) patients with renal or ureteral malformation, ureteral stricture (2) patients with urinary system swelling (3) combined with pyelonephritis and uretertis and other upper urinary tract infections Patients (4) combined with severe cardio cerebrovascular disease, liver, kidney and hematopoietic system severe primary disease (5) patients with hyperparathyroidism (6) allergic constitution 3. treatment methods: (1) treatment group: Huayu Jianpi prevention stone soup 1 bags a day 2 times a day, 4 weeks (2) control group: Huayu Jianpi prevention stone soup placebo once 1 bags a day 2 a day. Continued use of 4 weeks and 4. courses of treatment: 4 weeks 5. observation index (1) main curative effect index (group, medicine 4 weeks after examination, record one time): (1) 24 hours urination of citric acid, urine magnesium (ELISA) urine THP, OPN, ITIH3 protein expression (2) secondary curative effect index (group, medicine for 4 weeks after each test) 1) urine pH value in 24 hours urine urine The results of calcium, urine phosphorus, urine oxalic acid, urinary calcium, blood phosphorus, blood magnesium, blood uric acid: 1. comparability analysis: the age of two groups, the course of the disease, the ratio of men and women, urinary TH protein, osteopontin, a- trypsin inhibitor heavy chain H3, urine pH, 24 hours of urine calcium, urine phosphorus, urine oxalic acid, ururic acid, urinary magnesium, urinary citric acid, calcium, blood phosphorus, blood magnesium, blood The difference of uric acid and TCM syndrome score was not statistically significant (P 0.05), and there was a comparable result of.2. effect analysis: 2.1 the main curative effect index 2.1.1 had a significant difference before and after treatment in the total total of 24 hours urinary citrate excretion in the treatment group (P0.01), and the ratio of the treatment group to the control group was compared with the control group after treatment. The difference was statistically significant (P0.01) the total amount of excretion of citric acid in.24 hours was significantly increased by.24 hours before treatment. There was no significant difference between the total and the control group before and after treatment (P0.05). There was no significant difference between the two groups after treatment (P0.05). The concentration of urine TH protein in the treatment group before and after treatment was statistically significant (P0.01). The difference in the comparison between the treatment group and the control group was also statistically significant (P0.05), the concentration of.TH protein was lower than that before the treatment. The difference of urine OPN protein concentration in the treatment group was not statistically significant (P 0.05). There was no significant difference between the treatment group and the control group (P0.05). The urinary alpha trypsin inhibitor heavy chain H3 concentration in the treatment group was significantly different in the treatment group before and after the treatment (P0.01). The difference of the comparison between the treatment group and the control group was also significant (P0.05). The concentration of a trypsin inhibitor heavy chain H3 concentration between the treatment group and the control group was also significant. The function of Huayu Jianpi anti stone soup can increase the excretion of urinary citric acid in small molecular calculi inhibitor, and can reduce the abnormal expression of urinary TH protein and urinary alpha trypsin inhibitor heavy chain H3 in patients with urinary calculi and the curative effect of.2.1.2 TCM syndrome score. Huayu Jianpi prevention stone soup can obviously reduce the TCM syndrome score in the treatment group, the total effective rate is 79.3%, compared with the placebo control group 28.6%, the difference has significant statistical significance (P0.01). It shows that the Huayu Jianpi anti stone decoction can improve the main clinical symptoms of qi stagnation and blood stasis spleen deficiency syndrome patients, and reduce the TCM syndrome score, To correct the Yi Chengshi constitution of blood stasis, spleen deficiency and dampness resistance. The secondary therapeutic effect index of urinary calculi was fundamentally prevented from the recurrence of.2.2 in the treatment group. The urine pH value of the treatment group was higher, compared with the pre treatment group, the difference was statistically significant (P0.01); the difference between the treatment group and the control group was statistically significant (P0.01). After treatment, the treatment group was significantly different from the treatment group. The difference in urine calcium in the treatment group was statistically significant (P0.01), and the difference was statistically significant (P0.01) compared with the control group (P0.01). The curative effect of 24 hours urine oxalic acid, urinic acid, urine phosphorus, blood calcium, blood phosphorus, blood magnesium, blood uric acid, and the comparison of the treatment group before and after treatment were not statistically different. Significance (P0.05). There was no significant difference between the treatment group and the control group (P0.05). It showed that the drug had no effect on the above indexes. The abnormal expression of alpha trypsin inhibitor heavy chain H3 in urine can improve the urine pH value and decrease the total excretion of urinary calcium by 24 hours. Meanwhile, the Huayu Jianpi anti stone decoction can improve the main clinical symptoms of qi stagnation and blood stasis, the main clinical symptoms of spleen deficiency syndrome, reduce the score of TCM syndrome, and correct the Yi Chengshi constitution of blood stasis, spleen deficiency and damp resistance. The Ming Huayu Jianpi anti stone decoction can regulate the concentration and expression of the main calculi inhibitors in urine of patients with urinary calculi, and have a certain metabolic regulation effect. These effects have important positive significance for the prevention of recurrence of urinary calculi. The study of anti stone soup should start with two aspects. First of all, although the prescription time is only 3 years, the clinical application also shows a good effect on preventing the recurrence of stone. However, the number of cases observed and the time of observation are short. So the curative effect needs a large sample, multi center, random control, the observation time is over 3 years. Secondly, the effect of Huayu Jianpi anti stone soup on the main stone inhibitors in human urine was observed, and the effect of its effect on the expression of stone inhibitor in the kidney tissue and the main mechanism of controlling the stone inhibitor were not understood. This requires a well-designed model animal test and in vitro crystal model inhibition test. Only in this way can we comprehensively evaluate the preventive effect of Huayu Jianpi anti stone soup on the recurrence of urinary calculi.
【學位授予單位】：中國中醫(yī)科學院
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R691.4

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相關(guān)期刊論文 前4條

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