CN114306499A - Application of Zhibai Dihuang pills in preparation of medicaments for preventing and treating cisplatin acute kidney injury - Google Patents
Application of Zhibai Dihuang pills in preparation of medicaments for preventing and treating cisplatin acute kidney injury Download PDFInfo
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Abstract
The invention discloses application of Zhibai Dihuang pills in preparation of a medicament for preventing and treating cisplatin acute kidney injury. The invention discusses the application of the Chinese patent medicine 'Zhibai Dihuang pill' for nourishing yin and reducing pathogenic fire to the alleviation of the cisplatin-induced acute kidney injury by using the Zhibai Dihuang pill on an in-vitro cell model and an in-vivo animal model of the cisplatin-induced acute kidney injury. The result shows that the acute kidney injury induced by the cisplatin can be obviously improved by using the Zhibai Dihuang pill for interventional therapy on an in-vivo model and an in-vitro model. The invention develops a new application for the utilization of the Zhibai Dihuang pills, expands the treatment range of the Zhibai Dihuang pills, and opens up a new traditional Chinese medicine treatment method for the cisplatin acute kidney injury disease.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to an application of Zhibai Dihuang pills in medicines for preventing and treating cisplatin acute kidney injury.
Background
Cisplatin (CDDP) is a first-line non-specific anti-tumor drug in clinical use, and is mainly used for treating various solid malignant tumors such as head and neck cancer, lung cancer, ovarian cancer, and the like. Cisplatin can cause cell death through a variety of pathways, the most important of which is interference with DNA replication synthesis, inducing cell death. However, the clinical use of cisplatin is limited due to severe toxic side effects. Among them, 25-40% of clinical patients develop kidney disease after cisplatin injection. The molecular mechanism of cisplatin-induced acute kidney injury is complex, and the existing research is mainly related to mechanisms such as oxidative stress, inflammation, hypoxia, vascular injury, apoptosis and the like.
At present, the medicine for effectively preventing and treating the cisplatin acute kidney injury is still lacked clinically. In recent years, hydration diuretics, vasodilators, antioxidants and the like are mainly used clinically to protect cisplatin from acute kidney injury. Therefore, the development of related medicaments capable of effectively improving the acute kidney injury induced by the cisplatin has important clinical significance.
The Chinese patent medicine is prepared into a Chinese medicine preparation for preventing and treating diseases by taking Chinese medicinal materials as raw materials and processing the Chinese medicinal materials into a certain preparation according to the theory of traditional Chinese medicine, and has the characteristics of stable property, definite curative effect, small toxic or side effect and the like. Because the pathogenesis of the cisplatin acute kidney injury is complex, the cisplatin acute kidney injury relates to multiple aspects, and the Chinese patent medicine can play a regulating role in multiple components, multiple targets and multiple ways. Therefore, the Chinese patent medicine has wide application prospect in preventing and treating cisplatin kidney injury.
Zhibai Dihuang Wan is a classic and famous prescription for nourishing yin and clearing heat, and is described for the first time in Jingyue quan Shu of Zhang Jingyue in the Ming Dynasty. In the formula, prepared rehmannia root is mainly used for nourishing blood and yin and tonifying spleen and kidney; corni fructus has effects of tonifying liver and kidney; poria has effects in invigorating spleen and tranquilizing mind; rhizoma Alismatis can eliminate internal heat; chinese yam has the effects of tonifying middle-jiao and spleen; cortex moutan, rhizoma anemarrhenae and cortex Phellodendri clear heat and eliminate dampness. The whole formula has the effects of nourishing liver and kidney, clearing heat and soothing nerves. The Zhibai Dihuang Wan is clinically applied to patients with deficiency of kidney yin, neurasthenia, hyperthyroidism, diabetes, hypertension, male infertility, anejaculation, recurrent hemospermia, nephrotic syndrome, urinary tract infection, prostatitis, climacteric syndrome, ototoxic symptoms caused by aminoglycoside drugs, refractory night sweat and the like which belong to the patients with hyperactivity of fire due to yin deficiency, and has obvious effects of treating and improving symptoms. Can also relieve fire excess due to yin deficiency caused by taking steroid hormone medicine.
In clinical research, the combined conventional therapy of Anemarrhena and phellodendron rehmannia pills can effectively improve the biochemical index level of patients with primary nephrotic syndrome and reduce the incidence rate of adverse reactions of patients (the analysis of the clinical curative effect of the combined conventional therapy of Anemarrhena and phellodendron rehmannia pills on primary nephrotic syndrome [ J ]. Chinese medical guidance, 2019,17(25): 174-175.). The pill of Anbai Dihuang combined with the tablet of Irbesartan can improve the renal function of patients with diabetic nephropathy and reduce the level of serum inflammatory factors (Nixianchun, Jiangjie, Zhang Xuguang, Zhuxiahong Anbai Dihuang pill combined with the clinical study on the treatment of diabetic nephropathy with Irbesartan [ J ] modern drugs and clinics, 2019,34(05): 1488-. Experimental studies have shown that Zhibai Dihuang Wan can prevent and treat Gentamicin (Hsu YH, Chen TH, Wu MY, Lin YF, Chen WL, Cheng TH, Chen CH.protective effects of Zhibai Dihuang Wan on crude structural afecta.J. Ethnopharmacol.2014; 151(1):635-42.), Aristolochic Acid (Lu PH, Lee HY, Liou YL, SF, Kuo KL, Chen YH.Nephroprotective Role of Zhibai Dihuang Wan in aromatic Acid-oxidized Zebroash. biomed Res. 202Dec 2; 2020: 5204348) induced damage by modulating apoptosis.
Through retrieval, no published document reports that the Zhibai Dihuang pill is used for preventing and treating cisplatin-induced acute kidney injury. The mechanism involved in the invention mainly comprises apoptosis and oxidative stress, and is verified from both cellular level and animal level.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provides the application of Zhibai Dihuang pills in the medicines for preventing and treating cisplatin acute kidney injury.
The technical scheme adopted by the invention for solving the technical problems is as follows:
application of Zhibai Dihuang Wan in preparation of medicaments for preventing and treating cisplatin acute kidney injury.
Furthermore, the application is the application of the Zhibai Dihuang pill in preparing or using the medicine for reducing the damage of cisplatin to normal kidney cells of a human.
Furthermore, the application is the application of the Zhibai Dihuang pills in preparing the medicine for reducing the apoptosis of the cisplatin-induced normal kidney cells of the human body.
Furthermore, the application is the application of the Zhibai Dihuang pills in preparing or using the medicine for relieving the oxidative stress of the cisplatin-induced normal kidney cells of the human.
Further, the application is the application of the Zhibai Dihuang pills in serving as or preparing medicines for treating the damage caused by the cisplatin to 293T and HK-2 cells in the normal kidney cells of the human body.
Further, the application is the application of the Zhibai Dihuang pill in preparing or preparing the medicine for relieving the acute kidney injury of the SD rat caused by the cisplatin.
Further, the application is the application of the Zhibai Dihuang pill in serving as or preparing a medicament for relieving weight loss of SD rats caused by cisplatin;
or the application is the application of the Zhibai Dihuang pill in serving as or preparing a medicine for restoring the increase of blood creatinine and blood urea nitrogen level of SD rats caused by cisplatin;
or the application is the application of the Zhibai Dihuang pills in preparing the medicine for restoring the kidney pathological damage of the SD rat caused by the cisplatin.
Furthermore, the application is the application of the Zhibai Dihuang pill in the aspect of being used as or preparing a medicament for preventing and treating the toxic and side effects of cisplatin;
or the application is the application of the Zhibai Dihuang pills in the aspect of being used as or preparing the medicine for preventing and treating the cisplatin nephrotoxicity.
Further, the Zhibai Dihuang pill comprises the following components: rhizoma anemarrhenae, cortex Phellodendri, radix rehmanniae Preparata, Corni fructus, cortex moutan, rhizoma Dioscoreae, Poria, Alismatis rhizoma, and adjuvants Mel;
the properties of the Zhibai Dihuang pill are as follows: brownish black water-honeyed pills are sweet and sour-bitter.
Furthermore, the daily taking dosage of the Zhibai Dihuang pill and the preparation thereof is equivalent to 4.08g of the original medicine.
The invention has the advantages and positive effects that:
1. the invention discusses the application of the Chinese patent medicine 'Zhibai Dihuang pill' for nourishing yin and reducing pathogenic fire to the alleviation of the cisplatin-induced acute kidney injury by using the Zhibai Dihuang pill on an in-vitro cell model and an in-vivo animal model of the cisplatin-induced acute kidney injury. The result shows that the acute kidney injury induced by the cisplatin can be obviously improved by using the Zhibai Dihuang pill for interventional therapy on an in-vivo model and an in-vitro model. The invention develops a new application for the utilization of the Zhibai Dihuang pills, expands the treatment range of the Zhibai Dihuang pills, and opens up a new traditional Chinese medicine treatment method for the cisplatin acute kidney injury disease.
2. The invention provides a Zhibai Dihuang pill which is prepared by improving cell injury, cell apoptosis and oxidative stress; improve the biochemical indexes and pathological changes of animals, and further reduce the acute kidney injury induced by the cisplatin. The Zhibai Dihuang Wan can play a role in preventing and treating the incidentally acute kidney injury through multiple ways and multiple target points.
3. The invention clarifies and verifies that the traditional Chinese medicine 'Zhibai Dihuang pill' for nourishing yin and reducing pathogenic fire has better effect of preventing and treating the acute kidney injury of cisplatin, provides experimental data support for the prevention and treatment of the clinical acute kidney injury of cisplatin, and also enlarges the treatment range of the 'Zhibai Dihuang pill'.
Drawings
FIG. 1 is a graph of the apoptotic flow cytometry analysis of 293T (A) and HK-2(B) cells of the present invention pretreated with Zhibai Dihuang pills for 24h and treated with cisplatin at 25 μ M for 24 h; wherein, A is an apoptosis flow analysis chart of 293T cells pretreated with Zhibai Dihuang pills of 100 mu g/mL for 24h and treated with cisplatin of 25 mu M for 24h, and B is an apoptosis flow analysis chart of HK-2 cells pretreated with Zhibai Dihuang pills of 100 mu g/mL for 24h and treated with cisplatin of 25 mu M for 24 h;
FIG. 2 is a quantitative graph of the flow cytometric analysis of 293T cell apoptosis in the present invention, wherein the Zhibai Dihuang Wan concentration is 100 μ g/mL, and the cisplatin concentration is 25 μ M. Comparison with blank group#P<0.05; comparison with cisplatin group<0.05；
FIG. 3 is a quantitative graph of the flow cytometric analysis of the apoptosis of HK-2 cells in the present invention, wherein the Zhibai Dihuang pill concentration is 100 μ g/mL, and the cisplatin concentration is 25 μ M. Comparison with blank group#P<0.05; comparison with cisplatin group<0.05；
FIG. 4 is a graph of the oxidative stress flow cytometry of 293T (A) and HK-2(B) cells pretreated with Zhibai Dihuang pills for 24h and cisplatin 25. mu.M for 24h in accordance with the present invention; wherein A is a cell oxidative stress flow analysis chart of 293T cells pretreated with Zhibai Dihuang pills of 100 mu g/mL for 24h and treated with cisplatin of 25 mu M for 24h, and B is a cell oxidative stress flow analysis chart of HK-2 cells pretreated with Zhibai Dihuang pills of 100 mu g/mL for 24h and treated with cisplatin of 25 mu M for 24 h;
FIG. 5 is a quantitative graph of the 293T cell oxidative stress flow cytometry analysis of the present invention, wherein the Zhibai Dihuang pill concentration is 100 μ g/mL, and the cisplatin concentration is 25 μ M. Comparison with blank group#P<0.05; comparison with cisplatin group<0.05；
FIG. 6 is a quantitative graph of the flow cytometry analysis of the oxidative stress of HK-2 cells in the present invention, wherein the Zhibai Dihuang pill concentration is 100 μ g/mL, and the cisplatin concentration is 25 μ M. Comparison with blank group#P<0.05; comparison with cisplatin group<0.05；
FIG. 7 is a histopathological staining of rat kidney in accordance with the present invention.
Detailed Description
The following detailed description of the embodiments of the present invention is provided for the purpose of illustration and not limitation, and should not be construed as limiting the scope of the invention.
The raw materials used in the invention are conventional commercial products unless otherwise specified; the methods used in the present invention are conventional in the art unless otherwise specified.
Application of Zhibai Dihuang Wan in preparation of medicaments for preventing and treating cisplatin acute kidney injury.
Preferably, the application is the application of the Zhibai Dihuang pill in preparing or using the medicine for reducing the damage of cisplatin to normal kidney cells of a human.
Preferably, the application is the application of the Zhibai Dihuang pill in preparing or using the medicine for reducing the apoptosis of the cisplatin-induced normal kidney cells of the human body.
Preferably, the application is the application of the Zhibai Dihuang pill in serving as or preparing a medicament for relieving cisplatin-induced oxidative stress of normal kidney cells of a human.
Preferably, the application is the application of the Zhibai Dihuang pill in serving as or preparing a medicament for the damage of cisplatin to 293T and HK-2 cells in human normal kidney cells.
Preferably, the application is the application of the Zhibai Dihuang pill in preparing or preparing the medicine for relieving the acute kidney injury of the SD rat caused by the cisplatin.
Preferably, the application is the application of the Zhibai Dihuang pill in serving as or preparing a medicament for relieving weight loss of SD rats caused by cisplatin;
or the application is the application of the Zhibai Dihuang pill in serving as or preparing a medicine for restoring the increase of blood creatinine and blood urea nitrogen level of SD rats caused by cisplatin;
or the application is the application of the Zhibai Dihuang pills in preparing the medicine for restoring the kidney pathological damage of the SD rat caused by the cisplatin.
Preferably, the application is the application of the Zhibai Dihuang pill in the aspect of being used as or preparing a medicament for preventing and treating the toxic and side effects of cisplatin;
or the application is the application of the Zhibai Dihuang pills in the aspect of being used as or preparing the medicine for preventing and treating the cisplatin nephrotoxicity.
Preferably, the Zhibai Dihuang pill comprises the following components: rhizoma anemarrhenae, cortex Phellodendri, radix rehmanniae Preparata, Corni fructus, cortex moutan, rhizoma Dioscoreae, Poria, Alismatis rhizoma, and adjuvants Mel;
the properties of the Zhibai Dihuang pill are as follows: brownish black water-honeyed pills are sweet and sour-bitter.
Preferably, the daily taking dosage of the Zhibai Dihuang pill and the preparation thereof is equivalent to 4.08g of the original medicine.
Specifically, the preparation and detection examples are as follows:
the biomaterials, drugs and test methods used in the present invention were as follows:
the cell lines used include human tubular epithelial cells HK-2, human embryonic kidney cells 293T.
The animals used were healthy SD male rats, SPF grade, 6-8 weeks old.
The pharmaceutical cisplatin standards used were purchased from MCE, CAS: 15663-27-1. Dissolving in culture medium, and making into appropriate concentration.
The specification of the pill (water-honeyed pill) of Zhibai Dihuang is as follows: every 100 grains weigh 20g, purchased from pharmaceutical factory, national standard of medicine, of Beijing Tongrentang science and technology development GmbH: z11020152.
The components: rhizoma anemarrhenae, cortex Phellodendri, radix rehmanniae Preparata, Corni fructus (preparata), cortex moutan, rhizoma Dioscoreae, Poria, Alismatis rhizoma, and Mel as adjuvant.
The characteristics are as follows: the product is brown-black water-honeyed pill; sweet and sour.
The efficacy is as follows: to nourish yin and reduce pathogenic fire.
Pulverizing pill of rhizoma anemarrhenae, cortex Phellodendri, rehmanniae radix, dissolving with ultrapure water at 60 deg.C, centrifuging at 3000rpm for 10min, filtering the supernatant with 0.45 μm filter membrane, making into appropriate concentration, and diluting with ultrapure water to obtain appropriate concentration gradient.
Example (b):
1MTT (methanol to transfer) detection of influence of Zhibai Dihuang pills on cell viability
1.1 Experimental methods
HK-2 cells and 293T cells were placed in DMEM/F12 and DMEM low sugar cell culture medium containing 1% penicillin-streptomycin solution (double antibody), 10% fetal bovine serum, and 5% CO at 37 deg.C, respectively2Culturing in an incubator. The cells were digested with pancreatin, and then counted on a hemocytometer with the cell density adjusted to 5X 104cells/mL, seeded in 96-well plates and 100. mu.L of cell suspension added per well. 5% CO at 37 ℃2Culturing in culture medium for 24h, adding 0.5 μ L of medicinal liquid of ZHIBAIDIHUANG pill with different concentration gradients, 3 multiple wells for each medicinal concentration, blank well and control well, and culturing at 37 deg.C and 5% CO2After 48h incubation in medium, 20. mu.L of 5mg/mL MTT solution (in PBS, 0.22 μm filter sterilized) was added to each well and incubation continued for 4h to terminate the incubation. The culture supernatant in each well was carefully removed, 100. mu.L of DMSO was added to each well, the mixture was left at 37 ℃ for 10min to dissolve the purple crystals sufficiently, and the absorbance (OD value) of each well was measured by a microplate reader (570nm,630nm), and the cell survival rate was calculated according to the following formula.
Cell viability (%) - (experimental OD-blank OD)/(control OD-blank OD) × 100%
1.2 results of the experiment
The Zhibai Dihuang pill has no cytotoxic effect on 293T and HK-2 cells, and has no statistical difference (P >0.05) compared with a blank group. See table 1.
TABLE 1 comparison of cell viability of Zhibai Dihuang pills against 293T and HK-2 cells
2MTT (methyl thiazolyl tetrazolium) detection of influence of Zhibai Dihuang pills combined with cisplatin on cell proliferation capacity of normal kidney cells
2.1 Experimental methods
HK-2 cells and 293T cells were adjusted to a cell density of 5X 10, respectively4cells/mL, seeded at 96-well plates, 100. mu.L of cell suspension was added per well. 5% CO at 37 ℃2After culturing in a culture medium for 24h, respectively adding 0.5 mu L of Zhibai Dihuang pill liquid medicines with different concentration gradients in each hole, continuing culturing for 24h, respectively adding 25 mu M of cisplatin in each hole, 0.5 mu L of Cispla, setting 3 compound holes in each medicine concentration, simultaneously setting a blank hole and a control hole, after continuing culturing for 24h, adding 20 mu L of MTT solution with the concentration of 5mg/mL in each hole (prepared by PBS and filtered and sterilized by a 0.22 mu M filter membrane), continuing incubating for 4h, and terminating culturing. The culture supernatant in each well was carefully removed, 100. mu.L of MSO was added to each well, and the mixture was left at 37 ℃ for 10min to dissolve the purple crystal formazan sufficiently, and the absorbance (OD value) of each well was measured by a microplate reader (570nm,630nm), and the cell survival rate was calculated according to the following equation.
Cell viability (%) - (experimental OD-blank OD)/(control OD-blank OD) × 100%
2.2 results of the experiment
Compared with the blank group, the cisplatin 25 mu M acts for 24h to obviously reduce the cell viability of 293T and HK-2 cells (P < 0.05); after the Zhibai Dihuang pill is pretreated, the cell viability of two cells is obviously improved (P is less than 0.05), and the protection effect on cisplatin-induced injury is more obvious along with the increase of the Zhibai Dihuang pill dosage. See table 2.
TABLE 2 comparison of the protective action of Zhibai Dihuang Wan against cisplatin damage
3 annexin V-FITC/PI double staining method for detecting apoptosis condition by flow cytometry
3.1 Experimental methods
HK-2 and 293T cells were seeded in 6-well plates at 5X 10 per well, respectively4cells/mL, 2mL of cell suspension per well. 5% CO at 37 ℃2Culturing in culture medium for 24h, adding different concentration gradient rhizoma anemarrhenae, cortex Phellodendri, and rehmanniae radix pill medicinal liquid 10 μ L/well, culturing for 24h, adding 25 μ MCisplatin, 10 μ L per well, 2 replicate wells per drug concentration, and incubation continued for 24 h. After the drug incubation is finished, collecting the supernatant, digesting with pancreatin, centrifuging at 2500rpm for 5min to collect cells, adding 1 XPBS to resuspend the cells, centrifuging again, then resuspending the cells with 100 mu LBinding Buffer solution, adding 5 mu L annexin V-FITC staining solution, placing at room temperature in a dark place for 10min, adding 5 mu L PI staining solution, and placing at room temperature in a dark place for 5 min. After staining was complete, detection was performed using a flow cytometer.
3.2 results of the experiment
Compared with the blank group, the Zhibai Dihuang pill does not cause obvious apoptosis when acting on 293T and HK-2 cells for 48 hours; the Zhibai Dihuang pill inhibits the apoptosis caused by cisplatin 25 mu M after protecting 293T and HK-2 cells for 24h, and has statistical significance compared with the cisplatin group (P < 0.05). As shown in fig. 1 to 3.
4 DCFH-DA staining method for detecting oxidative stress of cells by flow cytometry
4.1 Experimental methods
HK-2 and 293T cells were seeded in 6-well plates at 5X 10 per well, respectively4cells/mL, 2mL of cell suspension per well. 5% CO at 37 ℃2Culturing in culture medium for 24h, adding 10 μ L of medicinal liquid of ZHIBAIDIHUANG pill, culturing for 24h, adding 25 μ M of cisplatin, 10 μ L of cisplatin, and setting 2 multiple wells for each concentration, and culturing for 24 h. After the drug incubation, the supernatant was collected, digested with trypsin, centrifuged at 2500rpm for 5min to collect cells, added with 1 × PBS to resuspend the cells, and centrifuged again. The DCFH-DA staining solution is diluted properly with serum-free medium, 1mL of staining solution is added to each group of cells, the cells are suspended by blowing, and the cells are placed on a constant temperature oscillator and shaken for 20min at 37 ℃. After staining, centrifugation was performed at 2500rpm for 5min, and the cells were resuspended in 1 XPBS for another centrifugation, and the cells were resuspended in 1 XPBS after centrifugation, and then detected by flow cytometry.
4.2 results of the experiment
Compared with the blank group, the Zhibai Dihuang pill does not cause obvious cell oxidative stress when acting on 293T and HK-2 cells for 48 hours; the Zhibai Dihuang pill inhibits the cell oxidative stress caused by cis-platinum 25 mu M after protecting 293T and HK-2 cells for 24 hours, and has statistical significance compared with the cis-platinum group (P is less than 0.05). As shown in fig. 4-6.
5 animal experiments
5.1 Experimental methods
5.1.1 Experimental drug configuration
Cisplatin is prepared into 10mg/kg with 0.9% physiological saline, and is prepared for use.
The Zhibai Dihuang pill is crushed and dissolved into suspension with the concentration of 4.32g/kg and 8.64g/kg by using 0.5 percent sodium carboxymethyl cellulose solution, and is prepared for use.
Curcumin is prepared by using 0.5 percent sodium carboxymethylcellulose to dissolve suspension with the concentration of 150 mg/kg.
5.1.2 establishment of cisplatin acute renal injury model
Rat cisplatin 10mg/kg induced rat cisplatin acute kidney injury model by single intraperitoneal injection.
5.1.3 grouping and administration
Healthy male SD rats 30 (6-8 weeks old) are randomly divided into five groups of a normal group, a model group, a Zhibai Dihuang pill low and high dose group and a curcumin group (positive control group) according to the weight, and each group comprises 6 rats, and the specific intervention scheme is as follows:
(1) normal group: rats were gavaged with 0.5% sodium carboxymethylcellulose solution for 10 consecutive days and injected intraperitoneally with 0.9% normal saline on day 7.
(2) Model group: rats were gavaged with 0.5% sodium carboxymethylcellulose solution for 10 consecutive days, and on day 7, acute kidney injury was induced in rats as in item "5.1.2".
(3) Zhibai Dihuang Wan (4.32 g/kg): the rats are continuously irrigated with the Zhibai Dihuang pill suspension of the stomach at the dose of 4.32g/kg/d for 10 days, and the item of '5.1.2' on the 7 th day induces the acute kidney injury of the rats.
(4) Zhibai Dihuang Wan (8.64 g/kg): the rat is continuously irrigated with the Zhibai Dihuang pill suspension of the stomach at the dose of 8.64g/kg/d for 10 days, and the acute kidney injury of the rat is induced according to the item of '5.1.2' on the 7 th day.
(5) Curcumin group (positive control group): the curcumin suspension is perfused into the rat at the dose of 150mg/kg/d for 10 consecutive days, and the acute kidney injury of the rat is induced according to the item of '5.1.2' on the 7 th day.
5.1.4 serum and Kidney sample Collection and index determination
After the intervention of each group of rats according to the scheme under the item '5.1.3', after fasting for 12h before the experiment, the rats are anesthetized, blood is collected from abdominal aorta, the abdominal aorta is centrifuged at 3500rpm and 4 ℃ for 15min at a high speed, serum samples are separated, and the serum creatinine and the blood urea nitrogen level are measured by the kit. The kidneys were removed from the rat and weighed. Storing the left kidney in 4% paraformaldehyde solution for pathological detection; the right kidney was stored at-80 ℃.
5.1.5 results of the experiment
The body weight changes of the rats are shown in table 3: the weight of the rats in the model group is obviously reduced (P <0.05), and the weight change of the rats is recovered after the rats are treated by low-dose and high-dose drugs of Zhibai Dihuang and positive drug curcumin (P < 0.05). The kidney of the rat is swelled after the cisplatin induction, the weight of the kidney is increased compared with the normal group, the kidney index is increased compared with the normal group (P is less than 0.05), and compared with the model group, the weight of the kidney of the rat is basically recovered after the Zhibai Dihuang pill is treated by high dose and positive drug curcumin (P is less than 0.05).
Compared with the model group (table 3), the low and high dose of Zhibai Dihuang pill and curcumin group have the advantages that the SCr level in the serum of rats is respectively reduced to 134.16 +/-6.55, 83.45 +/-17.61 and 114.82 +/-15.27 mu mol/L (P is less than 0.05); the BUN level in rat serum is respectively reduced to 13.99 +/-1.26, 3.39 +/-1.07 and 13.31 +/-1.40 mmol/L (P is less than 0.05), which shows that Zhibai Dihuang pills can relieve the biochemical change of acute kidney injury induced by cisplatin, and especially the kidney protection effect of Zhibai Dihuang pills with high dose is more obvious.
Compared with the blank group, as shown in fig. 7, the rat kidney has obvious pathological changes, mainly including inflammatory cell infiltration, tubular cell necrosis, tissue vacuolation and the like. Compared with the model group, the low and high dose of Zhibai Dihuang pill and the curcumin group have the advantages that the pathological changes of the kidney of the rat are relieved, and the obvious difference from the blank group is avoided.
TABLE 3 comparison of the protective action of Zhibai Dihuang Wan against cisplatin-induced renal injury in rats
The experimental results show that: the Zhibai Dihuang pill can inhibit the effect of kidney injury caused by taking cisplatin, and the Chinese patent medicine for nourishing yin and lowering fire, namely the Zhibai Dihuang pill, has good effect of preventing and treating acute kidney injury induced by the cisplatin, can obviously relieve the kidney injury caused by the cisplatin, and provides better experimental basis for clinically applying the Zhibai Dihuang pill to prevent and treat the acute kidney injury induced by the cisplatin.
Although the embodiments of the present invention have been disclosed for illustrative purposes, those skilled in the art will appreciate that: various substitutions, changes and modifications are possible without departing from the spirit and scope of the invention and the appended claims, and therefore the scope of the invention is not limited to the embodiments disclosed.
Claims (10)
1. Application of Zhibai Dihuang Wan in preparation of medicaments for preventing and treating cisplatin acute kidney injury.
2. Use according to claim 1, characterized in that: the application is the application of the Zhibai Dihuang pill in preparing or using the medicine for reducing the damage of cisplatin to normal kidney cells of a human body.
3. Use according to claim 2, characterized in that: the application is the application of the Zhibai Dihuang pill in preparing the medicine for reducing the apoptosis of the cisplatin-induced normal kidney cells of human.
4. Use according to claim 2, characterized in that: the application is the application of the Zhibai Dihuang pills in preparing the medicine for relieving the oxidative stress of the cisplatin-induced normal kidney cells of the human body.
5. Use according to any one of claims 2 to 4, characterized in that: the application is the application of the Zhibai Dihuang pills in preparing the medicine for treating the damage of the cisplatin to 293T and HK-2 cells in normal kidney cells of human.
6. Use according to claim 1, characterized in that: the application is the application of the Zhibai Dihuang pill in preparing or using the medicine for relieving the acute kidney injury of the SD rat caused by the cisplatin.
7. Use according to claim 6, characterized in that: the application is the application of the Zhibai Dihuang pill in preparing the medicine for relieving weight loss of SD rats caused by cisplatin;
or the application is the application of the Zhibai Dihuang pill in serving as or preparing a medicine for restoring the increase of blood creatinine and blood urea nitrogen level of SD rats caused by cisplatin;
or the application is the application of the Zhibai Dihuang pills in preparing the medicine for restoring the kidney pathological damage of the SD rat caused by the cisplatin.
8. Use according to claim 1, characterized in that: the application is the application of the Zhibai Dihuang pill in the aspect of being used as or preparing a medicament for preventing and treating the toxic and side effects of cisplatin;
or the application is the application of the Zhibai Dihuang pills in the aspect of being used as or preparing the medicine for preventing and treating the cisplatin nephrotoxicity.
9. Use according to claim 1, characterized in that: the Zhibai Dihuang pill comprises the following components: rhizoma anemarrhenae, cortex Phellodendri, radix rehmanniae Preparata, Corni fructus, cortex moutan, rhizoma Dioscoreae, Poria, Alismatis rhizoma, and adjuvants Mel;
the properties of the Zhibai Dihuang pill are as follows: brownish black water-honeyed pills are sweet and sour-bitter.
10. Use according to claim 1, characterized in that: the daily taking preparation amount of the Zhibai Dihuang pill and the preparation thereof is equivalent to 4.08g of the original medicine.
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| CN104666811A (en) * | 2013-11-30 | 2015-06-03 | 白杨 | Preparation method of pepsin treated APR (Anemarrhena, Phellodendrom and Rehmannia) oral liquid |
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| CN104666811A (en) * | 2013-11-30 | 2015-06-03 | 白杨 | Preparation method of pepsin treated APR (Anemarrhena, Phellodendrom and Rehmannia) oral liquid |
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