Traditional Chinese medicine for treating diabetic nephropathy and preparation method thereof

[0028] Example 1

[0029] A traditional Chinese medicine for the treatment of yang deficiency of the spleen and kidney, which is made of Chinese medicinal materials with the following weight ratios: 9 parts of fenugreek, 9 parts of astragalus, 5 parts of epimedium, 5 parts of psoralen, 4 parts of dogwood, cinnamon 4 parts, 3 parts of Coptis, 2 parts of Rhubarb.

[0030] The preparation method is as follows: Weigh Chinese medicinal materials according to the weight ratio, add Astragalus by weight to 8 times of water to extract 3 times, each time for 1 hour, collect the extract and concentrate it to a clear ointment with a relative density of 1.1; Add 6 times 60% ethanol to reflux and extract 2 times, 1 hour each time, collect the extract and concentrate to a clear ointment with a relative density of 1.1; first press the weight of fenugreek, epimedium, psoralen, dogwood, and cinnamon Add 8 times water to extract three times, each time for 1 hour, collect the extract and concentrate it to a clear cream with a relative density of 1.13, then add ethanol until the weight content of ethanol reaches 60%, let stand overnight, take the supernatant and concentrate to the relative density For 1.1 clearing ointment, combine the above three clearing ointments, continue to concentrate to a thick paste with a relative density of 1.38, add appropriate amount of mannitol and dextrin to granulate, dry, and make granules.

[0031] In the thick ointment obtained after extraction according to the above preparation method, after testing, the content of astragaloside IV reached 25.6mg/g, the content of emodin reached 8.9mg/g, the content of icariin reached 12.7mg/g, and the transfer rate ( The proportion of the total amount of test components in the thick ointment to the total amount of test components in the medicinal materials was 56.4%, 32.8% and 42.3% respectively. The extraction effect is significantly better than conventional methods.

[0032] Properties: This product is brown particles, bitter and slightly sweet.

[0033] Specification: 12g per bag

[0034] Dosage: One bag each time, 3 times a day.

[0035] Example 2 Study on the therapeutic effect of the present invention on rats with type 1 diabetic nephropathy

[0036] 1. Test substance, reference substance, reagent

[0037] 1.1 Test product: Example 1 drug, specification: 12g/bag; traits: this product is brown granular. Use an appropriate amount of double distilled water to make the concentration required for the experiment, and use it now.

[0038] 1.2 Reference substance 1: Benazepril hydrochloride tablets. Source: Beijing Novartis Pharmaceutical Co., Ltd. Specification: 10mg*14 tablets/box.

[0039] Reference substance 2: Jinkui Shenqi Pills. Source: Beijing Tongrentang Co., Ltd. Tongrentang Pharmaceutical Factory. Specification: 360 capsules/bottle.

[0040] Take Benazepril Hydrochloride Tablets and Jinkui Shenqi Pills with an appropriate amount of double distilled water to make the concentration required for the experiment, and prepare them for immediate use.

[0041] 1.3 Reagents: STZ (streptozotocin), provided by sigma; urea nitrogen kit, creatinine kit, provided by Nanjing Jiancheng Institute of Bioengineering; triglyceride kit, total cholesterol kit, high-density lipoprotein Cholesterol kit and low-density lipoprotein cholesterol kit were provided by Beijing Beihua Kangtai Clinical Reagent Co., Ltd.

[0042] 2. Experimental system

[0043] Experimental animals: Wistar rats, SPF grade, provided by Hubei Experimental Animal Research Center.

[0044] Number of animals: 130 males

[0045] Apparatus: JPS-6 Yicheng Beyond Blood Glucose Tester, purchased from Beijing Yicheng Bioelectronics Technology Co., Ltd.; FA1004 electronic balance, purchased from Shanghai Sunny Hengping Scientific Instrument Co., Ltd.; 754N UV Spectrophotometer, purchased from Shanghai Provided by Oppler Instrument Co., Ltd.; TGL-16A high-speed centrifuge, purchased from Changsha Pingfan Instrument Co., Ltd.

[0046] 3. Experimental design

[0047] Table 1 Experimental design table

[0048]

[0049] 4. STZ and the usage of the test product

[0050] 4.1 STZ usage: STZ is given by tail vein injection.

[0051] STZ injection preparation: use 0.1mol/L sodium citrate buffer to prepare to the required concentration before use, store in the dark, and use within 30 minutes.

[0052] 4.2 Usage of test product

[0053] Administration method: The test product is given by gavage (ig), and mixed well before administration.

[0054] The basis of the administration method: the clinical administration route of the present invention is oral. This experiment was carried out in the same way as clinical human medication.

[0055] Dosing frequency and period: once a day for 8 weeks.

[0056] Dosage:

[0057] ① Blank control group (distilled water): 0

[0058] ②Model group (distilled water): 0

[0059] ③ Positive control group 1 (benazepril hydrochloride tablets): the dose is 1*10 -3 g/kg

[0060] ④ Positive control group 2 (Jinkuishenqi pills): the dose is 1g/kg

[0061] ⑤The high-dose group of the present invention: the dose is 7.2g/kg;

[0062] ⑥The dose group of the present invention: the dose is 3.6g/kg;

[0063] ⑦The low-dose group of the present invention: the dose is 1.8g/kg.

[0064] 4.3 Dosing volume

[0065] ① Blank control group (distilled water): the volume is 5ml/kg;

[0066] ②Model group (distilled water): the volume is 5ml/kg;

[0067] ③ Positive control group 1 (benazepril hydrochloride tablets): the volume is 5ml/kg;

[0068] ④ Positive control group 2 (Jinkuishenqi Pill): the volume is 5ml/kg;

[0069] ⑤ The high-dose group of the present invention: the volume is 5ml/kg;

[0070] ⑥The dose group of the present invention: the volume is 5ml/kg;

[0071] ⑦The low-dose group of the present invention: the volume is 5ml/kg.

[0072] Dosage basis: According to the clinical dosing instructions of the present invention, "orally administered three times a day, one bag each time", the clinical dose is 36g/60kg person/day, and the person kilogram body weight dose is 0.6g/kg; at the same time, According to the animal dose conversion table of the fourth edition of "Pharmacological Experimental Methods" (People's Medical Publishing House), the equivalent dose for rats is 6 times that for humans, which is 3.6g/kg. This equivalent dose is the experimental dose, and the low and medium doses are 1/2 and 2 times the equivalent dose respectively.

[0073] 5. Testing indicators

[0074] 5.1 Observation during modeling

[0075] Cage observation: All animals are observed at least once a day. Observations include all animals during the experiment. Observations include but are not limited to: skin, hair, eyes, ears, nose, mouth, chest, abdomen, external genitalia, limbs and Feet, respiratory tract and circulatory system, autonomous effects (such as salivation), nervous system (such as tremor, convulsions, stress response and abnormal behavior). At the same time, observe the rats' morbidity, mortality, damage and feeding, water supply, urination, defecation and other conditions. Animals with poor health should be marked and further observed, and euthanized if necessary according to the SOP.

[0076] Detailed clinical observation: After STZ was administered for one week, the fasting blood glucose of rats was measured every three days, and the average value of two consecutive fasting blood glucose measurements was calculated. When the average fasting blood glucose of rats was> At 16.65mmol/L, it can be regarded as a type 1 diabetic rat. After 3 weeks of diabetes, a metabolic cage was placed every 5 days to collect urine for 24 hours, and the kit was used to detect urinary microalbumin. Two consecutive urine detections of urinary albumin were regarded as rats with diabetic nephropathy.

[0077] 5.2 Observation after administration

[0078] The animal body weight and fasting blood glucose values ​​of rats were measured weekly (fasting for 12 hours before blood glucose measurement). Urine was collected for 24 hours every two weeks to determine the amount of urine albumin. After the experiment, blood was taken from the eyeball to measure the serum urea nitrogen (BUN) and creatinine (Scr) content; the heart was taken to measure triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL-C) and high 4 indicators of density lipoprotein (HDL-C) (the animal is fasted without water for 12 hours the day before blood collection). After weighing the animal’s kidney, it is stored in a 10% neutral formaldehyde solution, cellulose stained and HE stained for morphology Observed.

[0079] 6. Experimental results

[0080] 6.1 Effect of the present invention on the general state of type 1 diabetes rat model

[0081] Rats in the model group are sluggish, with dry hair, slower activities, increased drinking and diet, increased urine output, and various complications such as retinopathy in the later stage. The above conditions of the rats in the treatment group of the present invention have been improved to varying degrees.

[0082] 6.2 Effect of the present invention on the body weight of type 1 diabetic rat model

[0083] After the tail vein injection of STZ, the weight of the model group was significantly reduced, resulting in the model group's weight significantly lower than the blank control group at the 9th week. The body weight of the rats in the treatment group of the present invention increased from the second week of administration (the 10th week of the experiment), and the body weight of the rats in the treatment group of the present invention increased compared with the model group at the 9th week. More obvious. The weight of the positive control group of Benazepril Hydrochloride and Jinkui Shenqi Pills increased compared with the model group, but there was no significant difference. The results show that the present invention can alleviate the weight loss caused by type 1 diabetic nephropathy, as shown in Table 2.

[0084] Table 2 The influence of the present invention on the body weight of type 1 diabetic rat model

[0085]

[0086] Note: Compared with the normal group **P <0.05, compared with the model group △△ P <0.05, unit g)

[0087] Specific groups represented by English letters:

[0088] K: Blank control group; M: Model control group; Y: Benazepril hydrochloride tablets positive control group

[0089] J: Jinkui Shenqi Pill positive control group; G: High-dose group of the present invention; Z: Middle-dose group of the present invention

[0090] D: The low-dose group of the present invention.

[0091] 6.3 Effect of the present invention on blood sugar of type 1 diabetic rat model

[0092] Three days after the injection of STZ, the blood glucose of the model group was significantly higher than that of the blank control group, and the blood glucose of the model group remained basically unchanged until the end of the experiment; after eight weeks of treatment, the blood glucose of the rats in the treatment group of the present invention remained basically the same as before. There is no significant difference between the model groups. The blood glucose of the positive control group of benazepril hydrochloride and the positive control group of Jinkuishenqi pill remained basically unchanged from before administration. The results show that the present invention and the two positive drugs have no obvious effect on the hyperglycemia of type 1 diabetic nephropathy. See figure 1. This result is similar to the result of type 2 diabetes rat model.

[0093] 6.4 Effect of the present invention on urine protein in type 1 diabetic rat model

[0094] Eight weeks after STZ injection, the 24h urine protein of the model group was significantly higher than that of the blank control group (P <0.05). With the extension of time, the 24h urine protein of the model group gradually increased; four weeks after the administration of the present invention, the 24h urine protein of the rats was lower than that of the model group. Eight weeks after the administration of the present invention, the high, medium and low The 24h urine protein of rats in the dose group was significantly lower than that in the model group. After eight weeks of administration, the positive control group of Benazepril Hydrochloride and Jinkuishenqi Pills also significantly reduced the 24h urine protein of rats. The results show that the present invention can significantly reduce the 24-hour urine protein content of type 1 diabetic nephropathy model rats, and has a certain protective effect on the kidneys. The results are shown in Table 3. This result is similar to the result of type 2 diabetic nephropathy rat model.

[0095] Table 3 Effect of the present invention on urine protein in type 1 diabetic rat model

[0096] Group

[0097] Note: Compared with the normal group **P <0.05, compared with the model group △△ P <0.05.

[0098] The specific groups represented by the English letters are the same as in Table 2.

[0099] 6.5 Effect of the present invention on various biochemical indexes in serum of type 1 diabetic rat model

[0100] After the experiment, the contents of BUN, Scr, TG, LDL-C and HDL-C in serum of rats were determined. The results showed that there was no significant difference in Scr between the model group and the blank group, and the administration of the present invention and positive drugs had no significant effect on rats; the BUN of the model group was significantly higher than that of the blank control group (P <0.05). Eight weeks after administration of the present invention, the BUN of the rats in the high, medium, and low dose groups of the present invention was significantly higher than that of the model group. The BUN of the positive control group of Benazepril Hydrochloride and Jinkui Shenqi Pills was not significant compared with the model group. Sexual difference.

[0101] Compared with the blank control group, there were no significant changes in serum TG, TC, HDL-C, and LDL-C levels in the model group. This result showed that there was no abnormality in lipid metabolism in the animal model of type 1 diabetic nephropathy This result is different from that of type 2 diabetic nephropathy. The experimental results are shown in Table 4.

[0102] Table 4 The influence of the present invention on the serum biochemical indexes of type 1 diabetic rat model

[0103]

[0104] Note: Compared with the normal group *P <0.01, compared with the model group △ P <0.01.

[0105] The specific groups represented by the English letters are the same as in Table 2.

[0106] 6.6 The influence of the present invention on the pathological structure and organ index of the kidney in type 1 DN rat model

[0107] At the end of the experiment, HE and Masson staining were performed on rat kidneys in each group. The results showed that the cytoplasm of renal tubular epithelial cells in the model group was transparent, glycogen accumulated in a large amount, and extensive glycogen degeneration appeared, and mild fibrosis occurred at the same time. Compared with the model group, the renal glycogen deposition in the positive control group of Benazepril Hydrochloride and Jinkui Shenqi Pills was improved; the HE staining results of the high, medium and low dose groups of the present invention showed no significant improvement in the kidney structure, and all showed glycogen degeneration. . Masson staining showed that there was no obvious fibrosis in the high-dose group of the present invention, and mild fibrosis in the middle and low-dose groups. In the positive drug control group, the benazepril hydrochloride group had no obvious fibrosis, and the Jinkuishenqi Pill group There is mild fibrosis. (see image 3 )

[0108] The kidney organ index of the model group was significantly higher than that of the blank control group. The kidney index of the high-dose and middle-dose groups of the present invention and the positive drug control group did not significantly improve, and the low-dose group of the present invention was significantly lower than the model group. (see figure 2 )

[0109] The results show that the present invention has no obvious protective effect on kidney glycogen degeneration in type 1 diabetic nephropathy model rats; the high dose of the present invention can slow down the fibrosis of the kidney.

[0110] 8. Experimental conclusion

[0111] This experimental model adopts a one-time high-dose injection of STZ (streptozotocin) to induce the type 1 diabetes model in rats, which will eventually cause kidney disease and produce a diabetic nephropathy model.

[0112] Similar to type 2 diabetic nephropathy, type 1 diabetic nephropathy is caused by long-term hyperglycemia, which leads to changes in renal hemodynamics and activation of cytokines, which leads to the proliferation of renal mesangial cells, increased extracellular matrix, glomerular sclerosis and basement membrane Thickening and serious glycogen deposition can cause kidney glycogen degeneration. The clinical manifestations are mainly increased glomerular filtration rate, proteinuria, hypertension, and renal insufficiency (appearance of proteinuria). The current clinical diagnosis is mainly based on the detection of urine protein.

[0113] The experimental results show that ① the present invention can significantly ameliorate the symptoms of fatigue, dry hair, and retardation in rats caused by type 1 diabetic nephropathy; ② the present invention can resist the weight loss of rats caused by type 1 diabetic nephropathy to a certain extent; ③ Both the present invention and the positive control drug can significantly reduce the 24h urine protein content of type 1 diabetic nephropathy rats; ④The high, medium and low doses of the present invention have no improvement on the increase of serum BUN and Scr in type 1 diabetic nephropathy rats; ⑤HE staining shows The present invention does not significantly improve the renal glycogen degeneration in type 1 diabetic nephropathy, and cannot improve the damage of the kidney structure in type 1 diabetic nephropathy; ⑥Experimental results show that there is no disorder in lipid metabolism in type 1 diabetic nephropathy, TG, TC No significant changes have occurred in other related indicators; ⑦The experimental results also show that the present invention and the two positive drugs have no significant effect on reducing blood sugar in a rat model of type 1 diabetic nephropathy.

[0114] In summary, the present invention exerts a certain therapeutic effect on type 1 diabetic nephropathy by reducing urine protein in diabetic nephropathy rats and inhibiting renal tubulointerstitial fibrosis in a dose-dependent manner. This effect is equivalent to benazepril hydrochloride tablets, but stronger than gold. Kuishenqi pills.

[0115] Example 3 Research on the therapeutic effect of the present invention on rats with type 2 diabetic nephropathy 1. Test substance, reference substance, solvent, reagent

[0116] 1.1 Test product: Example 1 drug, specification: 12g/bag; traits: this product is brown granular. Use an appropriate amount of double distilled water to make the concentration required for the experiment, and use it now.

[0117] 1.2 Reference substance 1: Benazepril hydrochloride tablets. Source: Beijing Novartis Pharmaceutical Co., Ltd. Specification: 10mg*14 tablets/box.

[0118] Reference substance 2: Jinkui Shenqi Pills. Source: Beijing Tongrentang Co., Ltd. Tongrentang Pharmaceutical Factory. Specification: 360 capsules/bottle.

[0119] Take Benazepril Hydrochloride Tablets and Jinkui Shenqi Pills with an appropriate amount of double distilled water to make the concentration required for the experiment, and prepare them for immediate use.

[0120] 1.3 Reagents: STZ (streptozotocin), provided by Sigma; urea nitrogen kit, creatinine kit, provided by Nanjing Jiancheng Institute of Bioengineering; triglyceride kit, total cholesterol kit, high-density lipoprotein Cholesterol kit and low-density lipoprotein cholesterol kit were provided by Beijing Beihua Kangtai Clinical Reagent Co., Ltd.

[0121] 2. Experimental system

[0122] Same as Example 2.

[0123] 3. Experimental design

[0124] Table 5 Experimental Design Table

[0125]

[0126] 4. STZ and the usage of the test product

[0127] Same as Example 2.

[0128] 5. Testing indicators

[0129] 5.1 Observation during modeling

[0130] Cage side observation: the same as in Example 2.

[0131] Detailed clinical observation: After STZ was administered for one week, the fasting blood glucose of rats was measured every three days, and the average value of two consecutive fasting blood glucose measurements was calculated. When the average fasting blood glucose of rats was> 11.1mmol/L can be regarded as type 2 diabetic rats. After 3 weeks of diabetes, a metabolic cage was placed every 5 days to collect urine for 24 hours, and the kit was used to detect urinary microalbumin. Two consecutive urine detections of urinary albumin were regarded as rats with diabetic nephropathy.

[0132] 5.2 Observation after administration

[0133] Same as Example 2.

[0134] 6. Experimental results

[0135] 6.1 Effect of the present invention on the general state of type 2 diabetes rat model

[0136] Rats in the model group are sluggish, with dry hair, slower activities, increased drinking and diet, increased urine output, and various complications such as retinopathy in the later stage. The above conditions of the rats in the treatment group of the present invention have been improved to varying degrees.

[0137] 6.2 Effect of the present invention on the body weight of type 2 diabetes rat model

[0138] After four weeks of high-sugar and high-fat feeding, the weight of rats in the model group was significantly higher than that of the blank control group (P <0.05), the weight of the model group decreased significantly after STZ injection. The body weight of the rats in the treatment group of the present invention increased from the second week of administration (the 12th week of the experiment), and the body weight of the high-dose group of the present invention was significantly higher than that of the model group at the 8th week of administration. The weight of the benazepril hydrochloride positive control group increased compared with the model group, and the weight of the Jinkuishenqi Pill positive group remained basically unchanged from before administration. The results show that the present invention can alleviate weight loss caused by type 2 diabetic nephropathy, as shown in Table 6.

[0139] Table 6 The influence of the present invention on the body weight of type 2 diabetic nephropathy rats

[0140]

[0141] Note: Compared with the normal group **P <0.05, compared with the model group △△ P <0.05, unit g

[0142] The specific groups represented by the English letters are the same as in Table 2.

[0143] 6.3 Effect of the present invention on blood sugar of type 2 diabetic rat model

[0144] Three days after the injection of STZ, the blood glucose of the model group was significantly higher than that of the blank control group, and the blood glucose of the model group remained basically unchanged until the end of the experiment; after eight weeks of treatment, the blood glucose of the rats in the treatment group of the present invention remained basically the same as before. There is no significant difference between the model groups. The blood glucose of the positive control group of benazepril hydrochloride and the positive control group of Jinkuishenqi pill remained basically unchanged from before administration. The results show that the present invention and the two positive drugs have no obvious effect on the hyperglycemia of type 2 diabetic nephropathy. See Figure 4.

[0145] 6.4 Effect of the present invention on urine protein in type 2 diabetic rat model

[0146] Four weeks after STZ injection, the 24h urine protein of the model group was significantly higher than that of the blank control group (P <0.05). With the prolongation of time, the 24h urine protein of the model group gradually increased; after two weeks of administration of the present invention, the 24h urine protein of rats was lower than that of the model group. After eight weeks of administration of the present invention, high, medium and low doses The 24h urine protein of the rats in the group was significantly lower than that in the model group. After eight weeks of administration, the positive control group of Benazepril Hydrochloride and Jinkuishenqi Pills also significantly reduced the 24h urine protein of rats. The results show that the present invention can significantly reduce the 24-hour urine protein content of type 2 diabetic nephropathy model rats, and has a certain protective effect on the kidneys. The results are shown in Table 7.

[0147] Table 7 The influence of the present invention on urine protein in type 2 diabetic rat model

[0148] Group

[0149] Note: Compared with the normal group **P <0.05, compared with the model group △△ P <0.05

[0150] The specific groups represented by the English letters are the same as Table 2.

[0151] 6.5 Effect of the present invention on various biochemical indexes in serum of type 2 diabetic rat model

[0152] After the experiment, the contents of BUN, Scr, TG, LDL-C and HDL-C in serum of rats were determined. The results showed that there was no significant difference between the BUN of the model group and the blank group, and the administration of the present invention and positive drugs had no significant effect on rats; the Scr of the model group was significantly higher than that of the blank control group (P <0.05). Eight weeks after administration of the present invention, the Scr of the rats in the administration group was lower than that of the model group. The high-dose group was significantly lower than the model group. The Scr of the positive control group of Benazepril Hydrochloride and Jinkuishenqi Pill was also low. Compared with the model group, there is no significant difference; therefore, it is suggested that the present invention can significantly reduce Scr in type 2 diabetic nephropathy rats, and has a certain dose-dependence. The invention can protect the kidney function of type 2 diabetic nephropathy rats by increasing the glomerular creatinine filtration rate.

[0153] Compared with the blank control group, the serum TG content of the model group increased significantly, and the serum TC and HDL-C content had no significant changes compared with the blank group. After administering the present invention for eight weeks, the TG of rats in the high and medium dose groups was lower than that of the model group, the TG of rats in the benazepril hydrochloride group was slightly lower than that of the model group, and the TG of rats in the Jinkui Shenqi Pill group was higher than that of the model group; The serum LDL-C content of the group was significantly higher than that of the blank control group, and the administration group of the present invention was lower than the model group. The middle-dose group was the most obvious. The two positive control groups of Benazepril Hydrochloride and Jinkuishenqi Pills and the model group There is no significant difference in comparison. Therefore, the present invention can reduce the serum TG and LDL-C content of type 2 diabetic nephropathy rats, and has a quantitative effect relationship. This shows that the present invention can improve the lipid metabolism disorder in rats with type 2 diabetic nephropathy to a certain extent. The experimental results are shown in Table 8.

[0154] Table 8 The influence of the present invention on the serum biochemical indexes of type 2 diabetic rat model

[0155]

[0156] Note: Compared with the normal group **P <0.05, compared with the model group △△ P <0.05.

[0157] The specific groups represented by the English letters are the same as Table 2.

[0158] 7.6. The invention affects the pathological structure and organ index of the kidney in type 2 DN rat model

[0159] At the end of the experiment, HE and Masson staining were performed on rat kidneys in each group. The results showed that in the model group, the glomeruli were lobulated and the mesangial matrix increased (black arrow); the glomerulus was severely fibrotic, capillary was blocked, and the structure was unclear (green arrow); the cytoplasm of renal tubular epithelial cells was transparent. It is concentrated glycogen (red arrow); Masson staining shows that the glomeruli are lobulated and collagen fibers increase. The above conditions in the treatment group of the present invention were improved: the high-dose group HE and Masson staining both confirmed that the glomerular structure was basically normal, and no obvious abnormalities were seen; the medium-dose group HE showed that the glomerular capillary lumen was relatively smooth, with mild Masson staining showed that the glomeruli were lobulated and the collagen fibers were slightly increased. Both HE and Masson staining in the low-dose group confirmed mild glomerular fibrosis. Both HE and Masson staining of the Jinkui kidney-qi and benazepril hydrochloride positive control groups showed that glomerular capillaries were unobstructed, and mesangial cells and mesangial matrix did not increase. The results suggest that the present invention can prevent pathological damage of renal tissue structures such as glomerular sclerosis, fibrosis, and increased mesangial matrix in rats in type 2 diabetic nephropathy. see Image 6.

[0160] The kidney organ index of the model group was significantly higher than that of the blank control group, and administration of the present invention and the positive drug did not significantly improve the kidney index. (see Figure 5 )

[0161] 7. Experimental conclusion

[0162] Experimental results show that ① the present invention can significantly improve the symptoms of fatigue, dry hair, and retardation in rats caused by type 2 diabetic nephropathy; ② the present invention resists weight loss in rats caused by type 2 diabetic nephropathy, and is more effective than positive drugs , And has a quantitative effect relationship; ③The present invention and the positive control drug can significantly reduce the 24h urine protein content of type 2 diabetic nephropathy rats, suggesting that the present invention can protect the glomerular structure from damage; ④The present invention can significantly reduce The content of serum Scr in type 2 diabetic nephropathy rats is better than the positive control group, and has a quantitative effect, suggesting that the invention can protect the kidney function of type 2 diabetic nephropathy rats to a certain extent, and can increase the glomerular creatinine filtration rate ⑤HE and Masson staining show that the present invention and the two positive drugs can improve and even tissue type 2 diabetic nephropathy, increased renal mesangial matrix, glomerular fibrosis, glomerular lobules, increased collagen fibers and other pathological structural changes, thereby Protect the integrity of kidney structure and function. ⑥Compared with the two positive drugs, the present invention can reduce the serum TG and LDL-C content of type 2 diabetic nephropathy rats, and there is a certain dose-effect relationship, suggesting that the present invention can improve the lipid metabolism disorder in type 2 diabetic nephropathy rats to a certain extent; ⑦Experimental results also show that the present invention and the two positive drugs have no significant effect on reducing blood sugar in a rat model of type 2 diabetic nephropathy.

[0163] In summary, the present invention can play a certain therapeutic effect on rats with type 2 diabetic nephropathy by protecting kidney structure, reducing urine protein content, improving lipid metabolism disorders in the body, and the like.