The Effects Of Harpagoside On Renal Function In Chronic Renal Failure Rats

Chronic pain is the most common trouble in human life. For patients suffering from pain, chronic pain not only is a painful experience, but also brings a sense of loneliness and despair. Early treatment, effectively control and improvement of the quality of life are the ultimate clinical goals of treating chronic pain. Chronic pain includs bone and joint pain, back pain and neuropathic pain. In fact, whether in developing or developed countries, the incidence of chronic pain is very high. As we all know, chronic pain in chronic renal failure patients is one of common symptoms. Chronic pain caused by muscle, skeletal system disorders is especially prominent problem, and those suffering from muscular, skeletal system often are in the renal damage. For patients with chronic renal insufficiency there are more susceptible to adverse drug reactions.Drug treatment of chronic pain generally was analgesic drug acetaminophen, non-steroidal anti-inflammatory analgesic and opioids. Non-steroidal anti-inflammatory drugs have moderate analgesic effect on joint pain, muscle pain neuralgia and the other chronic pain, which owns better analgesia, better effects on inflammatory pain, and long-term application without addiction. Therefore, non-steroidal anti-inflammatory drugs as the main body of chronic pain analgesic is reasonable. Although in the past many of the post-marketing clinical research and drug assessment of NSAIDs observed its efficacy and toxicity, but the severity of these adverse reactions and the rate remain lacking of adequate quantitative data. In all of the adverse reactions, renal dysfunction that have more serious adverse reactions should be given adequate attention. Commonly used NSAIDs are often disabled or used with caution in patients with CRF; for NSAIDs to inhibit prostaglandin synthesis, which reduce the renal blood flow, particularly in the elderly, so the elderly long-term use of NSAIDs must be cautious. Provide a safe clinical drug of pain medication to CRF patients is an increasingly urgent need.In order to explore the effects of harpagoside and its mechanism of renal protection, we have established adenine-induced CRF animal model. We explored the effect of harpagoside on renal function through choicing the drug diclofenac acid having damaging effect on the renal function as a positive control drug and using harpagoside in different doses to CRF rats.This two-part set out below.PartⅠEstablishment of adenine induced chronic renal failure animal model in ratsObjective:Providing a safe pain medication to patients with CRF is the question in the treatment of clinical pain. Finding a kind of CRF animal model with good clinical correlation is important.Methods:SD male rats 52, adaptive feeding for 1 week, were randomly divided into normal group and model group. The normal group rats were given normal saline (5ml/d) daily by intragastric administration, The model groups rats were given adenine (250mg/kg/d) daily for 21 days by intragastric administration and reported on their general conditions.25% adenine were paired with saline concentration of suspension, At 22 day, We collected 24h urine using metabolic cages in order to test 24h urinary protein quantification. Plasma, urine and serum stored at-70℃were prepare for measuring BUN, Scr, Hb, Ca, P and other indexes. Right kidney saving in 10% formalin fixation, dehydration, dipping wax, embedded, sliced, for HE staining and Masson staining, and pathological changes were observed.Results:The rats of model group decreased food intake and lose weight. We found usual diet weight gain, and body hair smooth and shiny in normal rats. After 21 days model group compared with normal group have shown that kidney weight/body weight was increased,24h urine,24h urinary protein, BUN, Scr were increased significantly, Hb was decreased. The differences between normal group and model group were statistically significant (p<0.05).Conclusion:The adenine of intragastric administration could establish the appropriate CRF models in rats.PartⅡHarpagoside on the impact of chronic renal failureObjective:Harpagoside have the effects of anti-inflammatory, anti-rheumatic and analgesic. At present, harpagoside are often used in osteoarthritis, rheumatic diseases and chronic pain that can be used in patients with liver kidney metabolism. And NSAIDs, there are significant gastrointestinal, heart and kidney side effects. This part of the experiment on CRF animal model of rat can be investigated the renal protective effects of harpagoside and its possible mechanismMethods:32 CRF model rats were randomly divided into model group, Harpagoside low dose group, harpagoside high dose group, diclofenac group (n=8). Treatment with Harpagoside low-dose group (clinical equivalent groups 6 times than the adult dosage) by 302.4mg/(kg·d) was intragastric administered orally; high dose group (3 times than the low dose group) by 907.2mg/(kg·d) was intragastric adminitration. Diclofenac as positive control group paired with saline solution, according to 5.25mg/(kg·d) by intragastric administration. Normal group and model group were given normal saline.All groups were treated for 30 days,after 31 days we collected 24h urine with metabolic cages,24h urinary protein quantification was detected. Urine and serum saving in-70℃were prepared for measuring BUN, Scr, Hb, Ca, P and other indexes. Right kidney saving in 10% formalin fixation, dehydration, dipping wax, embedded, sliced, for HE staining and Masson staining, and pathological changes were observed in each group. TGF-β1 assay in renal tissue by SABC. In the course of treatment, rats eated and drunk freely.Results:The data collection were completed in 31st days, the During the treatment course of diclofenac 2 rats died. During the course of treatment, the model rats decreased food intake, weight loss, listlessness, dry hair missing. Normal diet in normal group rats, weight gain, body hair smooth and shiny. Harpagoside high and low dose group of 24h urine,24h urine protein and kidney weight/body weight, BUN, Scr, Hb, electrolytes were compared with model group, no significant difference between the two groups (p>0.05), high and low dose groups showed no significant difference (p>0.05); diclofenac group and model group were the values and harpagoside high and low groups were significantly different. In this study, kidney pathology and Masson staining of conventional table harpagoside low and high dose group kidney tissue changes and fibrosis were less severe degree, in the diclofenac group the injury of the kidney is most. In this study, immunohistochemistry showed TGF-β1 in harpagoside high and low dose groups were much less expression. Harpagoside did not further increase the renal tubular-interstitial damage, suggesting that, compared with diclofenac harpagoside is a safe, non-nephrotoxic drugs.Conclusion:This study shows that after 30 days in the CRF rats fed with low and high dose Harpagoside kidney weight/body weight and renal function are no further deterioration, anemia and electrolyte imbalance are not further aggravated. But in the CRF rats of diclofenac group, there have been two dead rats, after 30 days, renal function, anemia and electrolyte imbalance are further deterioration, In this study, immunohistochemistry showed TGF-β1 in harpagoside high and low dose group was much less expression than in the diclofenac group. Harpagoside may inhibit its expression in the kidney, which reduces the excessive accumulation of renal interstitial fibrosis. The effect of Harpagoside on the CRF may be related to decreased the expression of TGF-β1 in renal tissues.SummaryIn this paper, we use the classic model of CRF induced by the adenine. The results show that in the CRF rats fed with low and high dose Harpagoside,30 days later kidney weight/body weight, renal function did not deteriorate further more, anemia and electrolyte imbalance are not further aggravated. Masson staining of renal pathology shows in low and high dose group renal changes and fibrosis were less severe severe. In this study, immunohistochemistry showed TGF-β1 in harpagoside high and low dose group was much less expression than in the diclofenac group. Harpagoside may inhibit its expression in the kidney, which reduces its excessive accumulation of renal interstitial fibrosis. The effect of Harpagoside on the CRF may be related to decreased the expression of TGF-β1 in renal tissue.On current NSAIDs are often not used or used with caution in patients with CRF; so as to providing a safe drug in patients with CRF is the common problems in the clinical treatment of pain. The harpagoside for the clinical treatment of pain in patients with CRF is a safe choice of medication.