糖尿病大鼠罗库溴铵神经肌肉阻滞作用的药效学

doi:10.3881/j.issn.1000-503X.11169

Acta Academiae Medicinae Sinica

Acta Academiae Medicinae Sinica ›› 2019, Vol. 41 ›› Issue (2): 149-155.doi: 10.3881/j.issn.1000-503X.11169

• Original Articles • Previous Articles Next Articles

Neuromuscular Pharmacodynamics of Rocuronium in Diabetic Rats

LIU Xiaowen^1,²,GONG Ruisong³,LIU Zhen⁴,ZUO Jun^1,²,ZHAO Jing^1,²()

1 Graduate School,CAMS and PUMC,Beijing 100730,China
2 Department of Anesthesiology,China-Japan Friendship Hospital,Beijing 100029,China
3 Department of Anesthesiology,PUMC Hospital,CAMS and PUMC,Beijing 100730,China
4 Department of Anesthesiology,Beijing Hospital,Beijing 100730,China

Received:2019-01-14 Online:2019-04-28 Published:2019-05-07
Contact: Jing ZHAO E-mail:zhaojing1009@aliyun.com
Supported by:
Special Fund for Clinical Research of Chinese Medical Association(13081230508)

Abstract

Abstract:

Objective To investigate diabetes-mediated changes in the neuromuscular pharmacodynamics of rocuronium in rats.Methods Diabetes mellitus was induced by a single injection of streptozotocin in rats.A total of 24 male SD rats were assigned to four groups using random number table:the normal control group,diabetic 2-week group,diabetic 4-week group,and diabetic 8-week group(6 rats per group).The sciatic nerve was stimulated in a rain-of-four(TOF)pattern,and the twitch tension changes in the tibialis anterior muscle were demonstrated by mechanomyography after intravenous injection of rocuronium in vivo.The time course characteristics of rocuronium,including onset time,and the recovery time from rocuronium injection to TOF ratio 75%(RT75%)and 90%(RT90%),were recorded,and half maximal inhibitory concentration(IC₅₀)values of rocuronium were determined using a four-parameter dose response curve.Results Compared with the normal controls,the diabetic rats had significantly prolonged onset time of rocuronium,while the RT75% and RT90% were decreased at all rocuronium doses(P<0.001).The time course changes became increasingly significant as the duration of diabetes lengthened(P<0.001).The IC₅₀ and 95% confidence interval values for rocuronium in the normal control group,diabetic 2-week group,diabetic 4-week group,and diabetic 8-week group were 0.37(0.35-0.38)mg/kg,0.44(0.43-0.46)mg/kg,0.59(0.57-0.61)mg/kg,and 0.64(0.61-0.66)mg/kg,respectively.IC₅₀ values were significantly higher in the diabetic groups vs.normal control(P<0.001)and gradually increased as the duration of diabetes lengthened(P<0.001).Conclusion Diabetes is associated with the rat skeletal muscle hyposensitivity to rocuronium,which is featured by prolonged onset time of rocuronium,decreased RT 75% and RT 90%,and right shift of the cumulative dose-response curve of rocuronium.

Key words: diabetes mellitus, rocuronium, cumulative dose-response curve, half maximal inhibitory concentration, time course characteristics

CLC Number:

R614.2+4

LIU Xiaowen, GONG Ruisong, LIU Zhen, ZUO Jun, ZHAO Jing. Neuromuscular Pharmacodynamics of Rocuronium in Diabetic Rats[J].Acta Academiae Medicinae Sinica, 2019, 41(2): 149-155.

Figures/Tables 4

Table 1

Table 2

Table 3

Fig 1

References 21

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分组Group	罗库溴铵剂量Doses of rocuronium(mg/kg)
分组Group	0.2	0.3		0.4		0.5		0.6		0.7
正常对照组Normal control group	81.75±9.89	100.17±10.15		88.25±5.09		78.75±7.44		71.00±9.32		71.50±7.58
造模2周组Diabetic 2-week group	94.67±5.93	95.17±5.90		92.42±10.23		87.25±12.73		85.50±13.80		88.25±6.64
造模4周组Diabetic 4-week group	106.33±4.57	106.33±4.57		110.75±11.33		110.75±11.33		102.75±11.08		99.83±6.65
造模8周组Diabetic 8-week group	117.17±14.93	125.83±12.50		120.50±14.69		120.50±14.69		115.33±14.05		105.67±5.06
F	14.781	14.055		11.725		16.553		15.161		31.800
P	0.000	0.000		0.000		0.000		0.000		0.000
P1	0.192	0.296		0.515		0.287		0.319		0.002
P2	0.002	0.243		0.002		0.000		0.001		0.000
P3	0.000	0.000		0.000		0.000		0.000		0.000
分组Group	罗库溴铵剂量Doses of rocuronium(mg/kg)
分组Group	0.8		0.9		1.0		1.1		1.2
正常对照组Normal control group	67.50±4.20		70.08±8.15		69.58±4.72		62.17±7.92		40.60±3.09
造模2周组Diabetic 2-week group	94.08±4.71		80.25±6.18		78.50±5.59		75.25±6.29		62.83±5.19
造模4周组Diabetic 4-week group	98.17±7.43		92.50±7.42		90.50±7.80		87.92±12.17		77.50±3.32
造模8周组Diabetic 8-week group	108.00±8.70		102.92±6.09		98.92±4.81		97.67±9.55		81.75±8.02
F	42.112		24.980		29.206		14.781		14.055
P	0.000		0.000		0.000		0.000		0.000
P1	0.000		0.124		0.096		0.141		0.000
P2	0.000		0.000		0.000		0.001		0.000
P3	0.000		0.000		0.000		0.000		0.000

分组Group	罗库溴铵剂量Doses of rocuronium(mg/kg)
分组Group	0.2	0.3		0.4		0.5		0.6		0.7
正常对照组Normal control group	180.25±17.76	217.67±26.37		335.75±43.99		424.50±32.04		503.17±34.14		615.42±49.28
造模2周组Diabetic 2-week group	171.75±30.26	207.00±19.79		330.75±47.17		366.58±10.79		412.08±25.94		453.67±32.52
造模4周组Diabetic 4-week group	175.67±19.16	192.50±13.02		232.33±33.84		315.50±35.33		389.75±20.71		427.08±20.93
造模8周组Diabetic 8-week group	162.83±16.01	179.08±21.50		224.33±33.81		290.17±15.73		332.25±16.08		381.50±13.68
F	3.658	2.831		11.099		48.631		49.576		77.617
P	0.030	0.064		0.000		0.000		0.000		0.000
P1	0.007	0.018		0.004		0.001		0.000		0.000
P2	0.246	0.095		0.000		0.000		0.000		0.000
P3	0.020	0.022		0.000		0.000		0.000		0.000
分组Group	罗库溴铵剂量Doses of rocuronium(mg/kg)
分组Group	0.8		0.9		1.0		1.1		1.2
正常对照组Normal control group	615.42±49.28		683.83±67.48		768.00±69.33		869.08±59.79		969.75±66.22
造模2周组Diabetic 2-week group	507.00±22.86		559.50±28.59		678.00±25.05		789.83±46.73		796.00±60.25
造模4周组Diabetic 4-week group	478.33±20.44		516.00±30.47		580.00±32.93		654.33±15.49		699.75±41.83
造模8周组Diabetic 8-week group	408.17±13.26		457.92±32.87		478.00±20.40		503.58±31.61		540.83±65.79
F	54.082		58.031		162.627		112.291		65.898
P	0.000		0.000		0.000		0.000		0.000
P1	0.000		0.000		0.000		0.000		0.000
P2	0.000		0.000		0.000		0.000		0.000
P3	0.000		0.000		0.000		0.000		0.000

分组Group	罗库溴铵剂量(mg/kg) Doses of rocuronium(mg/kg)
分组Group	0.2	0.3		0.4		0.5		0.6		0.7
正常对照组Normal control group	352.00±41.58	431.17±57.16		575.33±31.08		721.33±33.45		853.42±43.51		965.25±35.47
造模2周组Diabetic 2-week group	287.42±29.48	378.50±33.31		484.00±47.65		649.67±27.54		754.25±48.71		810.00±47.94
造模4周组Diabetic 4-week group	326.17±49.61	395.17±16.63		449.08±35.25		562.08±39.98		636.67±36.06		703.92±37.87
造模8周组Diabetic 8-week group	297.42±23.31	380.33±20.02		427.42±68.70		511.25±28.34		608.00±24.69		653.17±29.84
F	0.708	3.963		13.711		32.117		47.935		60.483
P	0.559	0.023		0.000		0.000		0.000		0.000
P1	0.502	0.383		0.831		0.001		0.000		0.000
P2	0.716	0.048		0.000		0.000		0.000		0.000
P3	0.177	0.004		0.000		0.000		0.000		0.000
分组Group	罗库溴铵剂量(mg/kg) Doses of rocuronium(mg/kg)
分组Group	0.8		0.9		1.0		1.1		1.2
正常对照组Normal control group	965.25±35.47		1042.67±57.22		1193.58±49.36		1416.67±89.49		1565.50±123.96
造模2周组Diabetic 2-week group	828.58±45.52		867.08±41.15		1011.75±26.95		1084.83±55.98		1203.50±98.19
造模4周组Diabetic 4-week group	743.58±54.79		806.17±40.82		911.67±31.59		986.17±28.56		1054.58±57.71
造模8周组Diabetic 8-week group	678.83±21.45		740.00±18.71		792.83±9.22		844.75±26.22		902.83±31.71
F	50.220		29.878		54.090		88.326		54.874
P	0.000		0.000		0.000		0.000		0.000
P1	0.000		0.000		0.001		0.004		0.000
P2	0.000		0.000		0.000		0.000		0.000
P3	0.000		0.000		0.000		0.000		0.000

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