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Effect Of Qihuangbaoshen Granules On TGF-β1/ROS/MAPK Signaling Transduction Pathway In Renal Failure Juvenile Rats

Posted on:2016-10-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:M QinFull Text:PDF
GTID:1224330464460281Subject:Chinese medical science
Abstract/Summary:PDF Full Text Request
Objective:1. Unilateral ureteral ligation (UUO) method is used to copy a mouse pup model of renal failure, dynamic observation of Qihuangbaoshen particles in UUO were renal function and renal morphological changes and the degree of interstitial fibrosis.2. Dynamic observation of renal failure were TGF-product beta 1, oxidative stress and MAPK signal path expression, to explore the relationship between renal interstitial fibrosis with her pups.3. To investigate the Qihuangbaoshen particles antagonism to sustain the possible role of a mouse pup renal interstitial fibrosis mechanism, in order to help clinical.Method:4 weeks SD male rats of 240 were randomly divided into control group, model group, Qihuangbaoshen particles of low, medium and high dose group (hereinafter referred to as low, medium and high dose group) with the method of unilateral ureteral ligation replication were renal failure model, the impression is made after the start, the control group, model group gave his pups only to distilled water to fill the stomach, low, medium and high dose group were given were2g·kg-1 ·d-1、4g·kg-1 ·d-1、6g·kg-1 ·d-1 Qihuangbaoshen particles lavage, continue to fill the stomach 28 days, one day to 2 times, the daily 08:00 and 18:00 lavage.Respectively UUO postoperative 7,14,21 days, 28 days between groups are put to death pups only 10, each baby mice abdominal aorta in pursuance of law by 2 to 3 ml of blood, take that back supernatant fluid in serum creatinine and urea nitrogen content, quickly remove obstruction side kidney and observe the appearance of the kidney, saline after clean, part of the kidney tissue soaked in 10% foer Ma Linzhong fully cured, and observed pathological changes, immunohistochemical detection of TGF-beta 1 protein expression capacity, put in liquid nitrogen, the rest of part after kidney homogenate colorimetry to detect SOD, MDA, GSH enzyme-linked immunosorbent method test, ROS content, part of the extraction of total protein after Western blot method between groups were p-in the kidney tissues p38MAPK, pERK1/2, Nrf2, gamma GCS protein expression.Results:1.Compared with model group, stilbene Huang Bao kidney pellet each dose group were general condition is good, baby mice kidney failure level and signs is better than that of model group. Stilbene Huang Bao kidney pellet each dose group were the levels of serum creatinine, blood urea nitrogen at various time points are lower than the model group (P< 0.05, P< 0.01). The same point in time, stilbene Huang Bao renal particles dose groups were creatinine and urea nitrogen had the lowest levels. And medium dose group and high dose group of creatinine and urea nitrogen level, comparison between groups have no statistical significance (P> 0.05).2.Compared with model group, stilbene Huang Bao kidney pellet each dose group were obstruction side kidney swelling, water, and renal tubular atrophy are lighter, renal interstitial fibrosis area is relatively small.3.At each time point, stilbene Huang Bao renal particles in each dose group of baby mice kidney tissue homogenate MDA and ROS levels are lower than the model group, SOD and GSH levels at various time points are higher than that of model group, kidney tissues of Nrf2, gamma GCS protein expression was higher than that of model group (P< 0.05, P< 0.01). In the same point in time, the treatment group, the rats MDA and ROS level the lowest dose group, the rats SOD and GSH level the highest dose group, dose group of Nrf2 in the kidney tissues, gamma highest GCS protein expression (P <0.05, P< 0.01).4.The model group and treatment group were kidney tissues of TGF beta 1, p-p38MAPK, pERK1/2 expression with longer duration of o truction, increase gradually. Stilbene Huang Bao kidney pellet each dose group of TGF- beta 1, p-p38MAPK, pERK1/2 protein expression in various time points are lower than the model group (p< 0.05, p< 0.01). The same point in time, stilbene Huang Bao dose groups were renal tissues in the kidney particles of TGF-beta 1, p-p38MAPK, least pERK1/2 protein expression (p< 0.05, p< 0.01).Conclusion:1.Qihuangbaoshen particles to adjust renal failure were overall survival and reduce the content of serum creatinine and urea nitrogen.2.Qihuangbaoshen particles can reduce renal failure were renal pathological damage, reduce the damage of the renal tubules, relieve renal interstitial fibrosis.3.Qihuangbaoshen particles decreased renal failure were the expression of TGF-beta 1 protein in renal tissue.4.Qihuangbaoshen particless increased renal failure were Nrf2 in the kidney tissues, gamma GCS protein expression, increase the content of GSH and SOD, lower the content of MDA and ROS.5.Qihuangbaoshen particles lowered renal failure were phosphorylated p38MAPK in the kidney tissues and the expression of ERK1/2 protein.6.Qihuangbaoshen particles may by blocking renal failure were renal tissues TGF-beta 1/ROS/MAPK signal pathway conduction, thus inhibiting renal interstitial fibrosis, delay the renal failure.
Keywords/Search Tags:Renal interstitial fibrosis, Qihuangbaoshen particles, Transforming growth factor beta 1, Oxidative stress, Silk crack the original activated protein kinase
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