| Objective: This study was divided into two parts: animal experiment and clinical data to explore the effects of adrenocorticotropic hormone(ACTH),Huaiqi Huang granules and two drugs combined on adrenal cortex.To reduce the recurrence of children with frequently relaps nephrotic syndrome(FRNS)and steroid-dependent nephrotic syndrome(SDNS),and to provide experimental basis and optional treatment options.On the one hand,we compared the serum cortisol content,adrenal gland quality and adrenal index of Wistar rats,observed the pathological changes of adrenal cortex in rats to understand the effects of ACTH,Huaiqi Huang granules and two drugs combined on rat adrenal cortical function and morphology.On the other hand,by comparing FRNS and SDNS children with glucocorticoid(GC)dosage,adrenal cortex basic secretion function,adrenal cortex reserve function and the recurrence of children,to understand the effects of ACTH,Huaiqi Huang granules and two drugs combined on adrenal cortical function in children.Methods: 1.Grouping and intervention methods of experimental animals Fifty male Wistar rats were fed for 3 days to adapt the enviroment.The rats were randomly divided into 5 groups: blank control group,prednisone model group,Huaiqi Huang granules treatment group,ACTH treatment group and combined treatment group,10 rats in each group.The blank control group was fed with distilled water 10 m L/(kg·d),while the other four groups were treated with aqueous solution of prednisone acetate 12.5mg/(kg·d)in the morning 8 am,for 14 days,to make the model of the adrenal cortex inhibition in Wistar rats.After successful modeling,the blank control group and the prednisone model group were treated with the same way.The other three treatment groups were treated with prednisone acetate and then treated with drugs.Huaiqi Huang granules treatment group used Huaiqi Huang granules 4g/(kg · d)gavage.ACTH treatment group used ACTH 2U/(kg · d)subcutaneous injection.The combined treatment group plus ACTH and Huaiqi Huang granules,the same as above,continuous treatment for 14 days.The serum cortisol levels in rats were measured at the beginning of the experiment,on the 15 th day and the 29 th day of the experiment.On the 29 th day of the experiment,weighed the rats and sacrificed rats immediately after taking blood,and the bilateral adrenal glands were quickly removed.After weighing,the adrenal glands were placed in 10% formalin solution and further subjected to hematoxylin-eosin(HE)staining.2.Grouping and intervention of clinical FRNS and SDNS children Forty FRNS and SDNS children were randomly divided into control group,Huaiqi Huang granules treatment group,ACTH treatment group and combined treatment group,10 cases in each group.In the course of treatment,children in each group are based on the use of GC,used other drugs.The GC reduction followed the Guidelines[1] for the principle.Which we observed for 1 year.The control group was mainly treated with GC,rule reduction and the dose was re-adjusted when the disease relapses.Huaiqi Huang granules treatment group plus Huaiqi Huang granules for treatment.In the ACTH treatment group,ACTH was added before the frequently relaps(RF)or steroid-dependent(SD)dose of GC,and when the GC was reduced,ACTH was applied.After that,each reduction followed the above method until the GC was stopped.Combined treatment group plus Huaiqi Huang granules and ACTH,the treatment method as above.At the beginning of the experiment,six months after treatment and one year after treatment,the basic secretion and reserve function of adrenal cortisol in each group were measured,and the dosage of GC,relapse and adverse reaction were recorded.Results: 1.Animal experiment results 1.1 Serum cortisol content in each group At the beginning of the experiment,the serum cortisol levels in the five groups were not statistically significant(P>0.05).On the 15 th day of the experiment,the serum cortisol levels in the prednisone model group,Huaiqi Huang granules treatment group,ACTH treatment group and combined treatment group were significantly lower than those in the blank control group(P<0.05).But there was no significant difference between the four groups(P>0.05),suggesting that modeling success.On the 29 th day of experiment,serum cortisol levels in the Huaiqi Huang granules treatment group,ACTH treatment group and combination therapy group were higher than those in the prednisone model group,and the three groups were combined treatment group> ACTH treatment group> Huaiqi Huang granules treatment group(P<0.05).1.2 The adrenal gland quality and adrenal index were obtained On the 29 th day,the adrenal quality of Huaiqi Huang granules treatment group,ACTH treatment group and combined treatment group was higher than that of prednisone model group(P<0.05).Comparison between the three treatment groups,in addition to the combination therapy group and Huaiqi Huang granules treatment group the difference was statistically significant(P<0.05),there was no significant difference between the other groups(P>0.05).On the 29 th day of the experiment,the adrenal index of Huaiqi Huang granules treatment group,ACTH treatment group and combined treatment group was higher than that of prednisone model group(P<0.05),but there was no significant difference in adrenal index between the three groups(P>0.05).1.3 The results of HE staining of adrenal glands in each group The adrenal cortex of the blank control group was clear and neat.Prednisone model group compared with the blank control group adrenal cortex was thinning and disordered.Huaiqi Huang granules treatment group,ACTH treatment group and combined treatment group compared with prednisone model group,the adrenal cortex had different degrees of proliferation.And the proliferation of the combined treatment group was the most obvious.2.Clinical data results 2.1 The basic data of each group of children At the beginning of the experiment,there were no significant differences in gender,age and course of disease in the four groups(P>0.05)2.2 The results of the GC dose in each group Treatment for six months and treatment for one year,the dose of GC in ACTH treatment group and combination therapy group was significantly lower than that in control group(P<0.05).And the dose of GC in combination therapy group was lower than that in ACTH treatment group(P<0.05).In all treatment groups,treament for six months compared with before treatment,treatment for one year compared with before treatment and treatment for one year compared with the treatment for six months,the GC reduction was statistically significant(P <0.05).2.3 The results of the basic secretion of adrenal cortex in each group Treatment for six months and treatment for one year,the basic secretion of adrenal cortex in ACTH treatment group and combination therapy group was significantly higher than that in control group(P<0.05).And he basic secretion of adrenal cortex of the treatment group was higher than that of the ACTH treatment group(P<0.05).The basic secretion of adrenal cortex in ACTH treatment group and combination therapy group treament for six months compared with before treatment,treatment for one year compared with before treatment and treatment for one year compared with the treatment for six months was increased and statistically significant(P<0.05).And the basic secretion of adrenal cortex in Huaiqi Huang granules treatment group treament for six months compared with before treatment and treatment for one year compared with before treatment was increased and statistically significant(P<0.05).But the basic secretion of adrenal cortex in Huaiqi Huang granules treatment group treatment of one year compared with the treatment of six months was no statistically significant(P> 0.05).2.4 The results of the adrenal cortex reserve function in each group After 6 months of treatment and one year after treatment,the reserve function of adrenal cortex in ACTH group and combination therapy group were significantly higher than those in control group(P <0.05).But after six months of treatment,the function of adrenal cortex in Huaiqi Huang granules group was significantly higher than that in control group(P<0.05).The adrenal cortex reserve function in Huaiqi Huang granules treatment group,ACTH treatment group and combined treatment group treament for six months compared with before treatment,treatment for one year compared with before treatment and treatment for one year compared with the treatment for six months was changed and statistically significant(P <0.05). 2.5 The recurrence rate of each group of children and adverse reactions Treatment for six months and treatment a year later,the recurrence rate of the combined treatment group was statistically significant compared with the control group(P<0.008),the other groups were not statistically significant(P>0.008).In the course of treatment,there was no adverse reactions in the patients.Conclusions: 1.ACTH,Huaiqi Huang granules and the combination of two drugs could promote the secretion of endogenous cortisol in rats,promote the survival of the adrenal cortex of the adrenal cortex,improve its atrophy of the pathological morphology,and reduce the inhibition of GC on the rats adrenal cortex from both functional and morphological aspects.Among them,the combination therapy group was the most effective.2.ACTH,Huaiqi Huang granules and the combination of two drugs could reduce the inhibitory effect of GC on adrenal cortex in children with FRNS and SDNS,reduce the amount of GC in children,increase the level of adrenal cortex secretion and reserve function,ACTH and the combination of two drugs could reduce the recurrence rate,the effect of the combination of two drugs was significantly better than the individual medication. |
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