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Pharmacological Effects of Qi-Dan Fang on Nephrotic Syndrome

Author: YuYingJia
Tutor: ZhouJiuYao
School: Guangzhou University of Traditional Chinese Medicine
Course: Of Pharmacy
Keywords: Nephrotic syndrome Qi-Dan Fang nephrin podocin CD2AP mechanism
CLC: R285.5
Type: Master's thesis
Year: 2011
Downloads: 65
Quote: 0
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Abstract

Nephrotic syndrome (NS) is a set of clinical syndromes of glomerular disease which is caused by a variety of pathogens.It is not an independent disease and has four clinical symptoms:proteinuria、hyperlipidemia、hypoproteinemia and edema, especially the proteinuria. Hormone therapy is commonly used in NS treating, but it has much side effects and easily recrudesce. The traditional Chinese medicine, on the base of syndrome differentiation, shows satisfactory results on NS, especially the method of benefit Qi and active the Blood.This paper summarized the present study on pathophysiology, clinical treatment and animal models of NS, especially the structure and function of kidney podocyte molecules—nephrin、podocin and CD2AP, which are the key factors for NS and play an important role in the maintaining of glomerular podocyte structure and glomerular filtratsion function.In addition, the TCM theories of syndrome differentiation on NS were reviewed in this paper:the Spleen and Kidney Yang or Qi deficiency with Blood stasis is often taken for the main syndrome and the benefit Qi and active the Blood is the most important treatment. Astragalus is a typical kind of Chinese Qi-invigoratsing medicine and Salvia is a typical kind of Chinese blood-activating medicine according to the statistics on the medicine use in TCM,so the present study is to explore the prescription of Astragalus and Salvia (Qi-Dan Fang) and to determine its effects on NS to provide some related experimental researchs for its clinical treatment on NS, expand NS therapy, and provide a new approach to the exploration of high effective and low toxic therapy.Method:The NS rats was performed by tail -intravenous injection of adriamycin and be treated with Qi-Dan Fang.The therapeutic effect of Qi-Dan Fang on NS rats is evaluated by obsering the general condition and kidney pathological of NS rats and detecting some related indicators including urine protein,blood pressure, auricle microcirculation, serum albumin(TP), serum creatinine(SCr), blood urea nitrogen(BUN), total cholesterol(TC), triglycerides(TG), high-density lipoprotein (HDL) and low density lipoprotein(LDL). Meanwhile, determine the content of serum nitric oxide(NO), superoxide dismutase (SOD) and malondialdehyde(MDA); the total RNA is extract from each rats renal by Trizol reagent,and RT-PCR was used to determine the mRNA expression of the NS rats renal nephrin, podocin and CD2AP. All of these indicators were used to evaluate the therapeutic mechanism of Qi-Dan Fang on NS rats.The benefit Qi and active the Blood method plays an important role in the treatment of Qi-Dan Fang on NS, in addition, its promoting blood circulation、immune improving、anti-fatigue and anti-inflammatory effects correlated to the therapeutic effects on NS. To make a further research on the therapeutic effect of Qi-Dan Fang on NS rats, some other pharmacodynamic studies were conducted in this study:the blood stasis model established by injection of epinephrine with ice freezing to observe its promoting blood circulation effect by detecting the blood pressure, auricle microcirculation, serum nitric oxide(NO), superoxide dismutase (SOD), serum creatinine(Scr), total cholesterol(TC), triglycerides(TG), high-density lipoproteinl(HDL) and low density lipoprotein(LDL); the carbon particle clearance experiment to investigate its influence on the mice immune system; the models of ear swelling induced by dimethylbenzene and capillary permeability induced by acetic acid in mice to observe the anti-inflammatory effect; mice weight loading swimming method was used to study the anti-fatigue effect and to observe its effect on CK.Results:1. The therapeutic effect of Qi-Dan Fang on NS ratsRats in the Qi-Dan Fang treated groups possessed a better mental condition, raised movement and food intake and a better hair sheen,overall quality of life was greatly improved; the 24h urine protein of NS rats was obviously reduced(P<0.01), the renal function was improved and the elevation of blood pressure caused by NS was reduced (P<0.05); the high、middle and low dosage groups(12.34g/kg、6.17g/kg、3.09g/kg) could significantly improve the microcirculation of NS rats (P＜0.01 or P<0.05) and obviously decreased serum total cholesterol(TC) of NS rats (P<0.01); the high and middle dosage groups could reduce serum triglyceride(TG) of NS rats (P<0.05); each treatment group could improve serum high-density lipoprotein (HDL)level of NS rats(P<0.05) and increase the serum low density lipoprotein (LDL)level of NS rats (P＜0.01 or P<0.05); obviously improve the plasma protein level of NS rats (P＜0.01 or P＜0.05); reduce NS rats serum BUN level (P＜0.01 or P＜0.05); and obviously reduced serum Scr level of NS rats (P＜0.01 or P＜0.05); each treatment group could improve renal pathology condition of NS rats and restore glomerular structure inordinately.2. The therapy mechanism of Qi-Dan Fang on NS ratsQi-Dan Fang high、middle and low dosage groups could significantly improve the level of serum NO of NS rats (P＜0.01 or P＜0.05); significantly improve serum SOD activity of NS rats (P＜0.01 or P＜0.05); obviously reduce serum MDA level of NS rats (P＜0.01 or P＜0.05); improve the mRNA expressions of NS rats renal nephrin (P＜0.05) and obviously improve the mRNA expressions of podocin and CD2AP(P＜0.01). The occurrence of proteinuria in NS rats is closely related to the missing of renal nephrin、podocin、CD2AP, as RT-PCR showed the NS rats present a low mRNA expressions of nephrin, podocin and CD2AP. Qi-Dan Fang could significantly improve NS rats renal mRNA expression of nephrin (P＜0.05), and significant increase NS rats renal mRNA expression of podocin and CD2AP (P＜0.01), and proteinuria droping is positively correlated with the mRNA expression of nephrin, podocin and CD2AP.3. Other pharmacodynamic studies of Qi-Dan FangEach experimental group could significantly improve the auricle microcirculation status of stasis rats (P＜0.01); obviously improved the level of serum NO of stasis rats (P＜0.01); the high、middle and low dosage groups (12.34g/kg、6.17g/kg、3.09g/kg) could obviously increase the activity of serum SOD (P＜0.01 or P<0.05); reduce the serum total cholesterol (P＜0.01 or P＜0.05); obviously decrease the serum triglyceride (P＜0.01), raise the serum high-density lipoprotein (P＜0.01) and reduce the serum low-density lipoprotein content of stasis rats (P＜0.01 or P＜0.05). The high、middle and low dosage groups(24.66.34g/kg、12.33g/kg、6.165g/kg) of Qi-Dan Fang could significantly improve the mice immune function (P＜0.01 or P＜0.05); inhibit the xylene-induced ear swelling and the capillary permeability of mice(P＜0.01 or P＜0.05); obviously prolong the mice weight loading swimming time (P＜0.01 or P＜0.05) and obviously reduce the level of serum CK(P＜0.01 or P＜0.05).Conclusion:Qi-Dan Fang can improve NS symptoms such as reducing urinary protein of NS rats, reducing coagulation status, reducing serum BUN and SCr, and increasing the plasma protein level; improve NS rats airframe disease-resistant ability by improve the serum NO level and the cativity of the serum superoxide dismutase; promote the recovery of podocyte structure and improve the filtratsion ability of plasma protein by the means of enhancing the mRNA expressions of renal nephrin, podocin and CD2AP. Furthermore, it can strengthten the immunity and improve the body anti-fatigue capability and improve the blood stasis situation. In conclusion, the benefit Qi and active the Blood of Qi-Dan Fang is closely related to its functions on improving renal podocyte structure, reducing proteinuria occurrence and NS blood coagulation.And its therapeutic action on NS may stems from its role in improving renal podocyte molecules and restructuring its barrier function. And the NS pathogenesis is also closely related to the renal podocyte molecules.

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